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Dopamine and serotonin: Influences on male sexual behavior
Abstract
Steroid hormones regulate sexual behavior primarily by slow, genomically mediated effects. These effects are realized, in part, by enhancing the processing of relevant sensory stimuli, altering the synthesis, release, and/or receptors for neurotransmitters in integrative areas, and increasing the responsiveness of appropriate motor outputs. Dopamine has facilitative effects on sexual motivation, copulatory proficiency, and genital reflexes. Dopamine in the nigrostriatal tract influences motor activity; in the mesolimbic tract it activates numerous motivated behaviors, including copulation; in the medial preoptic area (MPOA) it controls genital reflexes, copulatory patterns, and specifically sexual motivation. Testosterone increases nitric oxide synthase in the MPOA; nitric oxide increases basal and female-stimulated dopamine release, which in turn facilitates copulation and genital reflexes. Serotonin (5-HT) is primarily inhibitory, although stimulation of 5-HT(2C) receptors increases erections and inhibits ejaculation, whereas stimulation of 5-HT(1A) receptors has the opposite effects: facilitation of ejaculation and, in some circumstances, inhibition of erection. 5-HT is released in the anterior lateral hypothalamus at the time of ejaculation. Microinjections of selective serotonin reuptake inhibitors there delay the onset of copulation and delay ejaculation after copulation begins. One means for this inhibition is a decrease in dopamine release in the mesolimbic tract.
... Chronic pain from migraine may directly damage vascular structures and cavernous nerves, involving a range of neurotransmitter dysregulation in the central nervous system (CNS), which may be a mechanism for inducing ED [32]. Chronic pain induces ED possibly through dysregulation of related neurotransmitter pathways [33]. Dysregulation of a range of processes in the CNS regulated by neurotransmitters may manifest as chronic pain. ...
... Dysregulation of a range of processes in the CNS regulated by neurotransmitters may manifest as chronic pain. Sexual motivation and mating behavior in men before and during sex are enhanced by the release of dopamine (a neurotransmitter) in many integrated parts [33]. One of the key pathogenic mechanisms of migraine is the dysregulation of the dopamine pathway, which causes ED [33]. ...
... Sexual motivation and mating behavior in men before and during sex are enhanced by the release of dopamine (a neurotransmitter) in many integrated parts [33]. One of the key pathogenic mechanisms of migraine is the dysregulation of the dopamine pathway, which causes ED [33]. Another study also reported that dysregulation of dopamine may be one of the potential mechanisms for the positive correlation between migraine and ED [34]. ...
Currently, few studies have explored the relationship between severe headache or migraine and erectile dysfunction (ED). The aim of our study was to assess the association between severe headache or migraine and ED in adult men in the US from the National Health and Nutrition Examination Survey (NHANES). We used data from two separate NHANES datasets for the analysis: 2001–2002 and 2003–2004. We used multiple logistic regression, subgroup analysis, and sensitivity analyses to assess the relationship between severe headache or migraine and ED. From 2001 to 2004, 3117 adult male participants (582 ED patients, 2535 non-ED patients) were identified. Categorical and continuous variables are described using counts and frequencies and means and standard errors, respectively. For continuous variables, the two groups were compared using survey-weighted linear regression, while for categorical variables, survey-weighted chi-square tests were performed. Multiple logistic regression analysis showed that in the fully adjusted Model 3, severe headache or migraine was statistically significantly associated with ED (OR 1.51; 95% CI 1.14–1.99; P = 0.0036). In the fully adjusted Model 3, the results of the subgroup analysis showed that an age of 40–60 years (OR = 1.55, 95% CI: 1.05, 2.31, P = 0.029), a body mass index (BMI) < 25 kg/m² (OR = 1.68, 95% CI: 1.02, 2.75, P = 0.0406) or ≥30 kg/m² (OR = 1.65, 95% CI: 1.07, 2.54, P = 0.022), hypertension (OR = 1.78, 95% CI: 1.22, 2.60, P = 0.0029), diabetes mellitus (OR = 1.71, 95% CI: 1.26, 2.31, P < 0.001), CVD (OR = 1.54, 95% CI: 1.12, 2.10, P = 0.011) and hyperlipidemia (OR = 1.83, 95% CI: 1.07, 3.13, P = 0.028) were associated with ED with severe headache or migraine. This study demonstrated a statistically significant association between severe headache or migraine and ED among adult men in the US. However, the results of the study should be interpreted with caution due to the failure to assess the effects of depression and anxiety on the outcomes.
... Testosterone, a key player in this scenario, is crucial for initiating sexual activities and fostering sexual desire and behavior. It also plays an essential role in regulating clitoral and vaginal physiology, facilitating genital lubrication, sensation, and engorgement [5]. Low levels of estrogen, on the other hand, are associated with dyspareunia and changes in vulvovaginal mucosa. ...
... While not explicitly addressed in the search results, progesterone is another hormone implicated in sexual desire. Progesterone receptors located in the hypothalamus, a key player in sexual desire regulation, suggest its potential role in modulating excitatory and inhibitory pathways in the brain, thereby impacting sexual desire [5]. The intricate web of neurotransmitters and peptides, such as serotonin, dopamine, and norepinephrine, further contributes to the physiology of sexual desire. ...
... The intricate web of neurotransmitters and peptides, such as serotonin, dopamine, and norepinephrine, further contributes to the physiology of sexual desire. HSDD may be linked to overactive inhibitory circuits in reward pathways, characterized by excessive serotonin activity and diminished dopamine activity [5]. Hormonal imbalances, encompassing changes in estrogen and progesterone levels, can result in shifts in sexual desire among women with HSDD. ...
Hypoactive Sexual Desire Disorder (HSDD) is a complex and multifaceted condition that significantly impacts the sexual well-being and overall quality of life of women. This comprehensive review aims to provide a holistic understanding of HSDD by exploring its etiology, diagnostic criteria, treatment approaches, and broader societal implications. The review delves into the intricate interplay of biological factors, including hormonal changes and neurotransmitter imbalances, that contribute to HSDD. Psychological factors, such as relationship issues, body image, and stress, are examined with sociocultural factors like societal norms, cultural influences, and media portrayals of sexuality. Diagnostic criteria and assessment methods, including The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria, and self-report questionnaires, are explored to facilitate accurate identification of HSDD and differentiation from other sexual disorders. The impact of HSDD on women's quality of life and relationships is examined, highlighting the emotional strain and interpersonal challenges associated with the disorder. Societal and personal consequences of untreated HSDD underscore the need for increased awareness and support. Treatment approaches encompass non-pharmacological interventions such as cognitive-behavioral therapy, sex therapy, and couples therapy and pharmacological interventions like hormone therapy and selective serotonin reuptake inhibitors. Novel treatments like bremelanotide, flibanserin, and integrative strategies combining psychotherapy and lifestyle changes are discussed. Challenges and controversies surrounding HSDD, including the lack of consensus on diagnostic criteria, debates about the medicalization of sexuality, ethical concerns regarding pharmaceutical interventions, and cultural considerations, are addressed. Future directions in research, including advances in neurobiological understanding, personalized medicine, long-term treatment studies, and destigmatization initiatives, offer promising pathways for enhancing the management of HSDD.
... Generally, a serotonergic tone is thought to inhibit sexual behavior [44]. In male rats, injecting 5-HT into the medial preoptic area of the hypothalamus impairs sexual behavior [57]. Furthermore, 5-HT is released from the anterior lateral hypothalamus when ejaculation Fig. 1. ...
... It is based on understanding a customer's needs, rapid prototyping, and the generation of novel ideas that will transform the way products, services, processes, and organizations are developed. occurs, ending the sexual cycle [57]. This inhibitory cycle may also lead to a decrease in dopamine, which enhances sexual function [30,62,83]. ...
... However, depending on the activated 5-HT receptor subtype, 5-HT may also enhance sexual behavior. Indeed, while 5-HT 1A receptor activation facilitates ejaculation, 5-HT 2C receptor activation inhibits ejaculations but facilitates erections [57]. . Since the 5-HT 1A receptor is downregulated and desensitized with chronic SSRI treatment, this may explain the reduced functionality of ejaculation. ...
Background:
Although Post-SSRI Sexual Dysfunction (PSSD) has finally been recognized by the European Medicines Agency as a medical condition that can outlast discontinuation of SSRI and SNRI antidepressants, this condition is still largely unknown by patients, doctors, and researchers, and hence, poorly understood, underdiagnosed, and undertreated.
Objective:
Becoming familiar with the symptomatology of PSSD and understanding the underlying mechanisms and treatment options.
Method:
We applied a design thinking approach to innovation to 1) provide insights into the medical condition as well as the personal needs and pains of a targeted patient; and 2) generate ideas for new solutions from the perspective of this particular patient. These insights and ideas informed a literature search on the potential pathophysiological mechanisms that could underlie the patient's symptoms.
Results:
The 55-year-old male patient developed symptoms of low libido, delayed ejaculation, erectile dysfunction, 'brain zaps', overactive bladder and urinary inconsistency after discontinuation of the SNRI venlafaxine. In many of these symptoms a dysregulation in serotonergic activity has been implicated, with an important role of 5-HT1A receptor downregulation and possible downstream effects on neurosteroid and oxytocin systems.
Conclusions:
The clinical presentation and development of symptoms are suggestive of PSSD but need further clinical elaboration. Further knowledge of post-treatment changes in serotonergic - and possibly noradrenergic - mechanisms is required to improve our understanding of the clinical complaints and to inform appropriate treatment regimes.
... Dopamine is a neurotransmitter produced in the brain under pleasurable and motivational conditions. Dopamine plays a significant role in facilitating the effects of copulatory efficiency, sexual behavior, and genital reflexes [20]. The significantly higher dopamine levels at the time of semen ejaculation could be attributed to the pleasure (although painful) stage, as ejaculation per se is not a painful phenomenon [1]. ...
Background and Aim: Electroejaculation (EE) is widely used for semen collection in bulls but raises concerns about animal welfare due to potential pain and stress. The physiological impact of EE on bulls remains a topic of debate, with previous studies yielding inconclusive results. This study aims to objectively evaluate pain and stress responses in bulls subjected to EE using electroencephalography (EEG) alongside hormonal, behavioral, and metabolite profiling. Materials and Methods: Eight bulls were subjected to EE in three replicates, with physiological and behavioral data collected before, during, and after the procedure. EEG parameters, including median frequency (MF) and total power (Ptot), were analyzed to assess cortical activity indicative of pain and stress. Blood samples were evaluated for stress-related hormones (adrenaline, noradrenaline, β-endorphin, and dopamine), while metabolomic analysis was conducted to identify biochemical alterations associated with stress. Behavioral indicators, including vocalization and muscle spasms, were recorded. Results: EE induced significant increases (p < 0.05) in stress hormones at ejaculation, which gradually returned to baseline 20 min post-procedure. EEG metrics, such as MF and Ptot, significantly increased during EE (p < 0.05), indicating heightened cortical activity associated with nociception. Metabolomic analysis revealed distinct biochemical shifts, with variations in glucose, taurine, and norepinephrine profiles across baseline, stimulation, and recovery phases. Behavioral observations corroborated physiological findings, with bulls exhibiting signs of discomfort, such as struggling, arched back posture, and excessive salivation. Conclusion: The combined EEG, hormonal, and metabolomic findings confirm that EE is a stressful and painful procedure for bulls. The study provides robust evidence of neurophysiological and biochemical responses indicative of pain. These findings highlight the need for alternative semen collection methods to minimize animal distress and improve welfare standards. Keywords: bulls, electroejaculation, electroencephalography, hormonal indicators, metabolomics, pain, stress.
... The mesolimbic dopamine system functions to promote reward seeking in naturalistic settings, for example, for food (Parada et al., 1990;Carelli et al., 2000;Wise, 2006;Nicola, 2016), water (Parada et al., 1990;Carelli et al., 2000), and sexual reward (Fibiger, 1993;Hull et al., 2004). Drugs of abuse are thought to overwhelm these processes, and cause long term plastic adaptations in these same reward-associated brain regions (Self, 2004;Koob, 2008;Tan et al., 2024). ...
Substance use disorder (SUD) is a chronic and relapse-prone neuropsychiatric disease characterized by impaired brain circuitry within multiple cell types and neural circuits. Recent advancements in single-cell transcriptomics, epigenetics, and neural circuit research have unveiled molecular and cellular alterations associated with SUD. These studies have provided valuable insights into the transcriptional and epigenetic regulation of neuronal and non-neuronal cells, particularly in the context of drug exposure. Critical factors influencing the susceptibility of individuals to SUD include the regulation of gene expression during early developmental stages, neuroadaptive responses to psychoactive substances, and gene–environment interactions. Here we briefly review some of these mechanisms underlying SUD, with an emphasis on their crucial roles in in neural plasticity and maintenance of addiction and relapse in neuronal and non-neuronal cell-types. We foresee the possibility of integrating multi-omics technologies to devise targeted and personalized therapeutic strategies aimed at both the prevention and treatment of SUD. By utilizing these advanced methodologies, we can gain a deeper understanding of the fundamental biology of SUD, paving the way for more effective interventions.
... Accumulated evidence indicates that the overall effect of 5-HT on ejaculation is inhibitory [194,195]. The role of 5-HT and the 5-HT system in sexual reflex was considered, based on data obtained from an experimental model with anesthetized rats, as a spinal ejection reflex [196]. ...
Prostate cancer (PCa) accounts for roughly 15% of diagnosed cancers among men, with disease incidence increasing worldwide. Age, family history and ethnicity, diet, physical activity, and chemoprevention all play a role in reducing PCa risk. The prostate is an exocrine gland that is characterized by its multi-functionality, being involved in reproductive aspects such as male ejaculation and orgasmic ecstasy, as well as playing key roles in the regulation of local and systemic concentrations of 5α-dihydrotestosterone. The increase in androgen receptors at the ventral prostate is the first elevated response induced by copulation. The regulation of prostate growth and function is mediated by an androgen-dependent mechanism. Binding 5-DHT to androgen receptors (AR) results in the formation of a 5α-DHT:AR complex. The interaction of the 5α-DHT:AR complex with the specific DNA enhancer element of androgen-regulated genes leads to the regulation of androgen-specific target genes to maintain prostate homeostasis. Consequently, ejaculation may play a significant role in the reduction of PCa risk. Thus, frequent ejaculation in the absence of risky sexual behavior is a possible approach for the prevention of PCa. In this review, we provide an insight into possible mechanisms regulating the impact of frequent ejaculation on reducing PCa risk.
... We speculate that the mechanism of action of SNRIs may be connected to the association between ED and the drug. SNRIs raise 5-HT and norepinephrine (NE) concentrations in the synaptic cleft, with 5-HT generally believed to inhibit male sexual behavior through somatic, parasympathetic, and sympathetic efferent processes [28,29]. Overconsumption of 5-HT can lower arousal and sexual desire, which can impact erectile function. ...
Aim
Serotonin‐norepinephrine reuptake inhibitors (SNRIs) have been extensively utilized for the treatment of depression and anxiety disorders. Clinical trials and real‐world data suggest that SNRIs may cause reproductive toxicity. To comprehensively assess this association, we conducted a pharmacovigilance study.
Methods
We utilized various disproportionality analysis algorithms, including reporting odds ratio (ROR), proportional reporting ratio (PRR), bayesian confidence propagation neural network (BCPNN), and multi‐item gamma poisson shrinker (MGPS), to assess the significance of reproductive toxicity‐related adverse events (AEs) reported to FDA Adverse Event Reporting System (FAERS) from January 2004 to December 2023, with subgroup analysis conducted by sex and age.
Results
Duloxetine and venlafaxine were associated with 14 and 25 AE signals related to reproductive toxicity, respectively, with erectile dysfunction (ED) and retrograde ejaculation identified as shared important medical events (IMEs). ED had the highest reporting frequency, strongest in venlafaxine‐treated patients under 45 years (ROR 4.34, PRR 4.33, IC 2.09, EBGM 4.25). Retrograde ejaculation was newly identified. With decreasing incidence, venlafaxine's median ED onset was 122.5 days and duloxetine's 38 days.
Conclusion
Our study provides evidence through an extensive analysis of the large‐scale real‐world FAERS database, aiding healthcare professionals in mitigating, and prioritizing SNRI‐related reproductive toxicity AEs.
... Phenylalanine and tyrosine are both precursors to dopamine, norepinephrine, and epinephrine (adrenaline). Dopamine activates motivated behaviors like copulation, controls genital reflexes, copulatory patterns and specifically sexual motivation (Hull et al., 2004), while norepinephrine, and epinephrine have been mooted as libido enhancers (Kayode and Yakubu, 2017). The reduction in the levels of testosterone and LH following clonidine administration in this research did not agree with previous studies. ...
... Furthermore, CB1 receptors are located within the dorsal raphe and ventral tegmental area, which are the nuclei containing the cell bodies for the serotonergic and dopaminergic input to the forebrain, respectively [9,19]. Activation of CB1 receptors is capable of modulating the synaptic release of both dopamine and serotonin, two neurotransmitters that are intricately involved in the regulation of genital reflexes, sexual motivation, and inhibition [5,13]. Thus, cannabinoids may modulate sexual function through direct regulation of the synaptic release of serotonin and dopamine. ...
Many women experience the effect of excess endocannabinoid production in the body by noticing some changes such as anxiety, the effect on learning and memory, reproduction and sex, metabolism, growth, and development. Others take cannabinoids as drugs. Cannabinoids are known to have anti-depressant properties but are also inhibitors of sexual urges. Research has shown that cannabinoids reduce dopamine levels, hence the need to inhibit the activities of cannabinoid receptors found all over the body, especially the brain. This research focuses on in-silico inhibition of cannabinoid receptors which serve as a precursor to the metabolism of cannabinoids. A Cannabinoid Receptor (CB1) PDB was downloaded (7V3Z) from https://www.rcsb.org. The protein was prepared, the sitemap identified and the receptor grid generated too. Tribulusamide D (TD) is a natural product isolated from Tribullus terrestris and has been confirmed to have anti-inflammatory activities. TD was drawn using the 2-D sketcher and copied to the 3-D workspace of the maestro Schrodinger suite. The native ligand, 2-[(1R,2R,5R)-5-hydroxy-2-(3-hydroxypropyl)cyclohexyl]-5-(2-methyloctan-2-yl)phenol was used as the reference drug (since it acts as an agonist to the receptor) and was prepared using ligprep module. The prepared protein and ligands were docked using the ligand docking module of the Maestro Schrodinger suite. The docking of the ligands with CB1 shows that Tribulusamide D has a better docking score with a higher negative value than the reference drug and hence could enhance sexual urge when the desire is inhibited by excess cannabi. In-vivo and in-vitro research is recommended to confirm the inhibitory activities of Tribulusamide D against CB1 as predicted by this study.
... The available evidence to date suggests that the general effect of serotonin on ejaculation is inhibitory. 40 In the nervous system, serotonergic activity is controlled by presynaptically located 5HT1A and 5HT1B autoreceptors and the SERT. When serotonin is released from axonal terminals, it binds to serotonin receptors and causes a wide range of effects. ...
In the light of existing literature, we reviewed the causes, management and potential therapeutic benefits of SSRI (Selective serotonin reuptake inhibitor) agents regarding sexual functions. (SSRIs) are the most commonly used medications for the treatment of depression, based on their effectiveness and safety profile. Sexual dysfunctions (SD) caused by SSRIs are one of the most important reasons for discontinuation of treatment in both genders. Knowing the intervention strategies in patients who develop SD is pivotal for the proper management of sexual side effects and the treatment adherence of patients. The effects of SSRIs on sexual functions can also be used to treat certain disorders. SSRIs have a high success rate in the treatment of premature ejaculation and their off-label use for this purpose is widely recognized.
... Additionally, since Esr2 expression was notably affected in the hypothalamus of exposed animals, it would be interesting to examine the effects of phthalate mixtures in noncopulatory behaviors, in particular anxiety and aggression, which have previously been associated with the deletion of ERβ [62]. Furthermore, other signaling pathways and molecules, such as serotonin and dopamine, which play crucial roles in sexual behavior [63], could be further investigated in future phthalate research. ...
Several phthalates, mainly used as plasticizers, are known for their adverse effects on the male genital system. Previously, we demonstrated that an environmentally relevant mixture of six antiandrogenic phthalates (PMix), derived from a biomonitoring study in pregnant Brazilian women, was able to disrupt the reproductive development in male rats. Experimental groups (control, 0.1, 0.5, and 500 mg PMix/kg/day) were established starting from the extrapolated human dose (0.1 mg/kg/day), followed by doses 5 times and 5000 times higher. Pregnant rats received daily oral gavage administration of either vehicle (control) or PMix from gestational day 13 to postnatal day 10. Here, we examined male and female offspring regarding changes in gene expression of key reproductive factors in the hypothalamus and pituitary gland at adulthood and conducted a battery of behavioral tests in males, including partner preference, sexual behavior, and male attractiveness tests. PMix induced some changes in mating‐related behavior in males, as demonstrated by the absence of preference for females against males and a higher number of penetrations up to ejaculation in the 0.5 dose group. PMix decreased Esr2 expression in the male hypothalamus across all three doses, and in females at mid and high doses in both the hypothalamus and pituitary. In male hypothalamus, we also observed decreased Kiss1 transcripts in these groups and a reduction in AR at the 0.5 dose group. In summary, our results provide further evidence that phthalates in a mixture, even at low doses, may exert cumulative effects on the structures underlying sexual behavior, which seems to be more sensitive than reproductive endpoints for the same experimental design.
... Phenylalanine and tyrosine are both precursors to dopamine, norepinephrine, and epinephrine (adrenaline). Dopamine activates motivated behaviors like copulation, controls genital reflexes, copulatory patterns and specifically sexual motivation (Hull et al., 2004), while norepinephrine, and epinephrine have been mooted as libido enhancers (Kayode and Yakubu, 2017). The reduction in the levels of testosterone and LH following clonidine administration in this research did not agree with previous studies. ...
Erectile dysfunction is characterized by an inability to obtain and sustain an erection good
enough for satisfactory sexual performance. The prevalence is 57.4% in Nigeria. The aim of this
research was to ascertain the acclaimed erectogenic potential of aqueous root extract of
Dichrostachys cinerea (AREDC). Thirty sexually experienced male Wistar rats were randomly
shared into 6 groups of 5 rats each (i.e. A - F). Group A served as positive control and received
distilled water only. Erectile dysfunction was induced in rats in groups B – F by oral
administration of clonidine (0.5 mg/kg body weight [BW]). The rats in groups B, C, D, E and F
were respectively treated with distilled water, sildenafil citrate (0.71 mg/kg BW) and AREDC at
50, 100 and 200 mg/kg BW. Animals were treated for 7 d and sacrificed 24 h after. Their penises
and blood were collected and prepared for the analysis of biochemical parameters of erectile
function. Phytochemical analysis showed the presence of alkaloids, flavonoids, zinc, arginine,
tyrosine and tryptophan. Clonidine administration reduced penile nitric oxide (pNO) and
increased penile phosphodiesterase V (pPDE5), but did not cause any alteration in penile
prostaglandin E1, serum dihydrotestosterone and penile RHO-kinase levels. However, AREDC
(200 mg/kg BW) reversed clonidine-induced decrease in pNO to positive control level. Extract
(all doses) also reduced clonidine-induced increase in pPDE5. Available results showed that
AREDC’s pro-erectile ability is owed to its inhibitory effect on pPDE5 and promotion of NO
synthesis in corpus cavernosum.
... In general, antidepressants produce a wide range of sexual side-effects that are related to their target neurotransmitter systems. Thus, antidepressants acting at the serotonergic system decrease rodent masculine (Olivier and Olivier 2019) and feminine (Clayton 2003;Clayton et al. 2014) sexual behavior, whereas antidepressants acting at catecholaminergic systems have the opposite effect (Hull et al. 2004;Olivier and Olivier 2019). Previous studies in male rats have shown that MTZ enhanced sexual motivation (Benelli et al. 2004), while VLF negatively affected sexual behavior (Bijlsma et al. 2014). ...
Rationale
Pharmacological treatments for depression are not always effective and produce unwanted side effects. Male and female sexual dysfunction is one of these side effects, which can lead to treatment withdrawal. Combination of two antidepressants with different mechanisms of action, like mirtazapine (MTZ) and venlafaxine (VLF) have been shown to be effective for treatment-resistant depression in humans. Combination of low doses of these drugs may still exert antidepressant-like effects without altering sexual behavior.
Objectives
To investigate the potential antidepressant-like effect of the chronic administration of low doses of MTZ plus VLF combined, as well as its impact on male and female sexual behavior in rats.
Methods
The antidepressant-like effect of a 14-day treatment with combinations of MTZ plus VLF (0/0, 2.5/3.75 or 5/7.5 mg/kg) was assessed in young adult male and female rats in the forced swim test (FST). The 5/7.5 mg/kg MTZ/VLF combination was also tested in the chronic mild stress (CMS) test, in both males and females treated for 21 days. The sexual effects of this last treatment were assessed in sexually experienced males and in gonadally-intact females during proestrus.
Results
The 5/7.5 mg/kg MTZ/VLF combination produced an antidepressant-like effect in the FST and reversed the CMS-induced anhedonia in both male and female rats. This combination did not alter male sexual behavior, female proceptive and receptive behaviors or the regularity of the estrous cycle.
Conclusion
The combination of low doses of MTZ and VLF might be a promising therapeutic alternative to treat depression without affecting the sexual response.
... According to studies, varying degrees of secretion of neurotransmitters, especially serotonin, result in significant changes in the mating rate of males. Serotonin (5-HT or 5-hydroxytryptamine hydrochloride) is a neurotransmitter that is produced by the hydroxylation and decarboxylation of tryptophan in the body and is essential for almost all living organisms (Hull et al., 2004;Hull and Dominguez, 2007). Meizel and Turner observed that serotonin induced an acrosomal reaction (AR) in capacitated sperm, implying the presence of a 5-HT-mediated receptor effect in the hamster sperm (Meizel and Turner, 1983). ...
Infertility affects 15% of all couples worldwide and 50% of cases of infertility are solely due to male factors. A decrease in motility in the semen is considered one of the main factors that is directly related to infertility. The use of supplementation to improve the overall sperm quality has become increasingly popular worldwide. The purpose of this study was to evaluate whether sperm motility was affected by the combination of serotonin (5-HT), selenium (Se), zinc (Zn), and vitamins D, and E supplementation. Semen samples were incubated for 75 min at 37°C in medium containing varying concentrations of 5-HT, Se, Zn, vitamin D, and E. 5-HT (200 μM), Se (2 μg/ml), Zn (10 μg/ml), vitamin D (100 nM), and vitamin E (2 mmol) have also been shown to increase progressive sperm motility. Three different mixtures of supplements were also tested for their combined effects on sperm motility and reactive oxygen species (ROS) production. While the total motility in the control group was 71.96%, this was found to increase to 82.85% in the first mixture. In contrast the average ROS level was 8.97% in the control group and decreased to 4.23% in the first mixture. Inclusion of a supplement cocktail (5-HT, Se, Zn, vitamins D and E) in sperm processing and culture medium could create an overall improvement in sperm motility while decreasing ROS levels during the incubation period. These molecules may enhance the success of assisted reproduction techniques when present in sperm preparation medium.
... The VTA is part of the reward circuit and one of the primary generators of DA in the brain. DA plays an important role in the regulation of male sexual behavior (Hull and Rodríguez-Manzo, 2009b) and it has been suggested that it improves sexual motivation and copulatory behavior (Beck et al., 2002) as well as genital reflexes (Hull et al., 2004). Another reason why we can see significant activation of the VTA in session 10 is because this structure is also related to movements during the execution of sexual behavior, that are displayed during the partner preference test. ...
Introduction
Different techniques have been used to identify the brain regions that control sexual motivation and sexual behavior. However, the influence of sexual experience on the activation of these brain regions in the same subject is unknown. Using manganese-enhanced magnetic resonance imaging (MEMRI), we analyzed the activation of brain regions in the sexual incentive motivation (SIM) and the partner preference PP (tests) on weeks 1, 5, and 10 in male rats tested for 10 weeks. AIM. In experiment 1, we analyzed the possible toxic effects of 16 mg/kg of MnCl2 on male sexual behavior, running wheel, and motor execution. In experiment 2, subjects were tested for SIM and PP using MEMRI.
Methods
In both experiments, a dose of 16 mg/kg (s.c) of chloride manganese (MnCl2) was administered 24 h before subjects were tested and placed immediately thereafter in a 7-Tesla Bruker scanner.
Results
In experiment 1, the dose of 16 mg/kg of MnCl2 did not induce behavioral alterations that could interfere with interpreting the imaging data. In experiment 2, we found a clear preference for the female in both the SIM and PP tests. We found a higher signal intensity in the olfactory bulb (OB) in week 1 of the SIM test compared to the control group. We also found increased signal intensity in the socio-sexual behavior and mesolimbic reward circuits in the SIM test in week 1. In the PP test, we found a higher signal intensity in the ventral tegmental area (VTA) in week 10 compared to the control group. In the same test, we found increased signal intensity in the socio-sexual and mesolimbic reward circuits in week 5 compared to the control group. Cohen's d analysis of the whole brain revealed that as the subjects gained sexual experience we observed a higher brain activation in the OB in the SIM group. The PP group showed higher brain activation in the cortex and subcortical structures as they acquired sexual experience.
Discussion
As the subjects gain sexual experience, more structures of the reward and socio-sexual circuits are recruited, resulting in different, and large brain activations.
... DA in the nigrostriatal tract influences motor activity, in the mesolimbic tract it activates behaviors including copulation, and in the medial preoptic area, DA controls genital reflexes, copulatory patterns, and sexual motivation. In addition, 5HT positively or negatively affects copulatory patterns such as erection and ejaculation by targeting a specific subtype of the 5HT receptors [50]. According to these studies, DA and 5HT strongly influence sexual behavior. ...
Drug addiction and its effect on the behavior and development of children has become a serious problem in our society. Methamphetamine (MA) is one of the most abused psychostimulants in the Czech Republic, and its abuse is rising worldwide. Previous studies have demonstrated the adverse long-term effects of maternal drug abuse on rat offspring. However, the father’s contribution as a parent and donor of half of the genetic information is unclear. Previous studies of other psychostimulant drugs indicate that long-term application of MA to adult male rats may induce changes in their reproductive system and lead to changes in rat pup functional and behavioral development. Therefore, the present review aimed to investigate the effect of MA administration on reproductive toxicity and sexual behavior of adult male rats, as well as the impact of paternal MA exposure on behavioral development and locomotor activity in rat offspring.
... DA in the nigrostriatal tract influences motor activity, in the mesolimbic tract it activates behaviors including copulation, and in the medial preoptic area, DA controls genital reflexes, copulatory patterns, and sexual motivation. In addition, 5HT positively or negatively affects copulatory patterns such as erection and ejaculation by targeting a specific subtype of the 5HT receptors [50]. According to these studies, DA and 5HT strongly influence sexual behavior. ...
... In contrast, serotonin and opioid peptides decrease activity in this circuit [19]. Several reports have shown that the activation of D2 receptors in the supraspinal ejaculation generator (SSEG) increases SEG excitability, while augmentation of 5-HT at these sites reduces SEG excitability [20,21]. The inhibitory effect of 5-HT on the neural circuit of ejaculation may explain the significant impact of chronic use of tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) [22]. ...
Background:
Hypericum species are widely acknowledged for their biological attributes, with notable attention being paid to Hypericum perforatum, commonly known as St. John's wort (SJW) within the Hypericum section of the Hypericaceae family. This species is among the most thoroughly investigated herbal medicines, particularly in terms of its application in the management of mild to moderate depression. SJW is used to treat depression, menopausal symptoms, attention-deficit hyperactivity disorder (ADHD), somatic symptom disorder, obsessive-compulsive disorder, and skin conditions, such as wounds and muscle pain. However, the usefulness and effectiveness of SJW for male sexual and reproductive health (SRH) are not well known.
Objective:
To assess the current evidence in the literature on the effect of SJW on male SRH.
Methods:
This narrative review followed a predetermined protocol and used MEDLINE and PubMed to identify articles published in English on the effects of SJW on male SRH. The search used various keywords, such as "Hypericum Perforatum", "St. John's Wort", and terms related to sexual and reproductive health issues. Articles published between the inception of the database and August 2023 were included.
Results:
We identified 12 articles published from 1999 to 2019, the majority of which were experimental and conducted on animals. These studies demonstrate variability in terms of design, sample size, type of SJW extract used, the dosage administered, and duration of treatment. Studies have indicated potential sexual dysfunction (SD) due to SJW, which includes reduced libido, delayed ejaculation, delayed orgasm, and erectile dysfunction. Additionally, reproductive toxicity has been suggested, as evidenced by spermicidal effects through the inhibition of sperm motility, abnormal spermatozoa, chromosomal aberrations, and DNA denaturation. Furthermore, some studies have reported potential adverse events during maternal exposure, inhibition of fertilization, and disruption of reproductive parameters.
Conclusions:
Our review suggests that the safety and efficacy of SJW in the treatment of human SRH remain unclear. Further comprehensive, well-designed studies with larger samples, longer exposure periods, and specific dosages are needed to clarify SJW's effects of SJW. Therefore, consultation with healthcare professionals before using herbal remedies or supplements is crucial.
... SSRIs work by blocking the reuptake of serotonin (5-HT) by the serotonin transporter, leading to an increase in the amount of 5-HT in the synaptic space 99 . Although the exact process is not fully understood, serotonin is widely believed to have a dampening effect on sexual function, whereas dopamine enhances it 100 . ...
Conditions referred to as 'male sexual dysfunctions' usually include erectile dysfunction, ejaculatory disorders and male hypogonadism. However, some less common male sexual disorders exist, which are under-recognized and under-treated, leading to considerable morbidity, with adverse effects on individuals' sexual health and relationships. Such conditions include post-finasteride syndrome, restless genital syndrome, post-orgasmic illness syndrome, post-selective serotonin reuptake inhibitor (SSRI) sexual dysfunction, hard-flaccid syndrome, sleep-related painful erections and post-retinoid sexual dysfunction. Information about these disorders usually originates from case-control trials or small case series; thus, the published literature is scarce. As the aetiology of these diseases has not been fully elucidated, the optimal investigational work-up and therapy are not well defined, and the available options cannot, therefore, adequately address patients' sexual problems and implement appropriate treatment. Thus, larger-scale studies - including prospective trials and comprehensive case registries - are crucial to better understand the aetiology, prevalence and clinical characteristics of these conditions. Furthermore, collaborative efforts among researchers, health-care professionals and patient advocacy groups will be essential in order to develop evidence-based guidelines and novel therapeutic approaches that can effectively address these disorders. By advancing our understanding and refining treatment strategies, we can strive towards improving the quality of life and fostering healthier sexual relationships for individuals suffering from these rare sexual disorders.
... Examples where a stimulus can be perceived as a positive challenge (i.e. a novelty, a stimulus that needs a response) are creative sexual practices such as: In this respect it is possible to create situations whereby a sexually-charged challenge increases sensory and mental activity. The novelty of the stimulation is perceived as a challenge by neurons and this may improve adaptation of neuronal function, and endorphin, dopamine and serotonin modulation (Uphouse, 2014, Hull et al., 2004. ...
Eroticism in later life is, on the whole, a taboo subject, and the stigma attached to expressions of sexual intent by older people is widespread in most cultures. However, sexuality and eroticism have an important role to play in maintaining healthy ageing. Sexuality is an essential aspect of our biology and its effects have repercussions in systems and organs other than the sexual. In this paper I review the importance of developing a sexual-erotic element in later life, an element that is intimately coupled with the phenomenon of hormesis. In hormesis, there is biological benefit following exposure to a mild stimulus or challenge, whereas exposure to a higher dose of the same stimulus becomes detrimental. Innovative sexual stimulation can be seen as a hormetic opportunity to initiate beneficial effects on the entire ageing human organism. The intention is to show that, health benefits may be obtained not only through physical (exercise), nutritional, mental or pharmacological challenges, but also through sexual stimulation of the appropriate magnitude and quality. By enhancing erotic stimulation it may be possible to experience many other benefits spanning several domains such as the endocrine, immune, circulatory and neurological. In addition, within an increasingly information-rich world, sexuality may play a part in improving adaptation to various cognitive external stimuli originating from our technological ecosystem.
... Neurotransmitters are a more likely explanation for these rapid effects. For example, dopamine can be released by sexual stimuli (Hull et al., 1999) and can increase sexual motivation (Hull, Muschamp, & Sato, 2004;Politis et al., 2013). Future studies could use functional neuroimaging (i.e., fMRI) to identify the neural correlates of these effects, and whether they involve targets of the midbrain dopamine systems. ...
A common life history theory trade-off is that which males face between mating effort and parental effort. This trade-off is observed across species, among individuals within a species, and within individuals across their lifespan. Recent studies suggest the possibility of more rapid trade-offs or motivational shifts in response
to transient aspects of the social environment. We were interested in whether exposure to matingrelated stimuli would negatively impact men's evaluation of parental-related stimuli and vice-versa, and whether this response would differ between fathers and non-fathers. In two separate experiments, a total of
160 heterosexual or bisexual men rated how appealing they found 40 images of attractive infants and 40 images of attractive adult females. Half of all participants viewed infant images before viewing female images, and the other half viewed female images before infant images. In both experiments, fathers rated infant stimuli
as more appealing than did non-fathers when infants were presented before females, but not when infants were presented after females. That is, priming fathers with female stimuli negatively impacted their ratings of infants. On the other hand, priming men with pictures of cute infants before viewing females did not impact ratings of female pictures, in either fathers or non-fathers. Nor did priming fathers with pictures of another highly rewarding stimulus - highly appealing foods - decrease their ratings of infants. The negative effect of female pictures on fathers' subsequent ratings of infant stimuli is consistent with the possibility that the female pictures activated motivational systems related to mating effort, which in turn inhibited motivational systems related to parental effort, rendering the infant stimuli less appealing. Our findings suggest that human fathers may be susceptible to transient shifts in life history strategy as a function of their immediate social environment.
... Also, since it has been established that testosterone enhances sexual interest, frequency of sexual acts and erections [76] and pelvic thrusting during copulation [77], the leadinduced decline in testosterone levels may inhibit these testosterone-dependent events. Furthermore, optimal levels of testosterone are essential for the synthesis and release of dopamine, another erectogenic neurotransmitter that facilitates sexual motivation and penile erection [78]. The reduced testosterone level causes a reduction in dopamine synthesis and release, impairment of dopamine-mediated activation of D2 receptors to stimulate NO synthase in the cell bodies of the paraventricular nucleus, and inefficient sexual motivation, urogenital reflexes, and penile erection [62]. ...
Aim
The present study evaluated the effect of lead exposure with and without zinc therapy on male sexual and erectile function.
Methods
Twenty male Wistar rats were randomly assigned into four groups; the control, zinc-treated, lead-exposed, lead + zinc-treated groups. Administrations were per os daily for 28 days.
Results
Zinc co-administration significantly improved absolute and relative penile weights and the latencies and frequencies of mount, intromission, and ejaculation in lead-exposed rats. Also, zinc ameliorated lead-induced reductions in motivation to mate and penile reflex/erection. These findings were accompanied by attenuation of lead-induced suppression of circulating nitric oxide (NO), penile cyclic guanosine monophosphate (cGMP), dopamine, serum luteinizing hormone, follicle-stimulating hormone, and testosterone. In addition, zinc alleviated lead-induced upregulation of penile activities of acetylcholinesterase and xanthine oxidase (XO), and uric acid (UA) and malondialdehyde (MDA) levels. Furthermore, zinc ameliorated the lead-induced decline in penile nuclear factor erythroid 2-related factor 2 (Nrf2) and reduced glutathione (GSH) levels, and catalase, superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione-S-transferase (GST) activities.
Conclusion
This study revealed that co-administration of zinc improves lead-induced sexual and erectile dysfunction by suppressing XO/UA-driven oxidative stress and upregulating testosterone via Nrf2-mediated signaling.
... The maintenance of optimal sexual and erectile function borders around effective testosterone-dopamine crosstalk [41]. Optimal levels of testosterone are essential in the synthesis and release of dopamine, which facilitates sexual motivation and penile erection [49]. The observed decline in dopamine and testosterone levels in HAART-treated animals agrees with and forms an extension of our previous study [11] which demonstrated a decline in circulating testosterone levels following HAART treatment. ...
Purpose
HAART has been shown to impair sexual function and penile erection via perturbation of penile redox balance, while zinc has been established to exert antioxidant activity. Therefore, this study focused on the role and associated molecular mechanism of zinc in HAART-induced sexual and erectile dysfunction.
Materials and methods
Twenty male Wistar rats were randomly grouped into four (n = 5 rats per group); the control, zinc-treated, HAART-treated, and HAART + zinc-treated groups. Treatments were per os daily for eight weeks.
Results
Zinc co-administration significantly improved HAART-induced increase in the latencies of mount, intromission, and ejaculations. Zinc also attenuated HAART-induced reduction in the motivation to mate, penile reflex/erection, and frequencies of mount, intromission, and ejaculations. In addition, zinc co-treatment improved HAART-induced decline in penile NO and cGMP, dopamine, and serum testosterone. More so, zinc prevented HAART-induced rise in penile activities of monoamine oxidase, acetylcholinesterase, phosphodiesterase-5, and arginase. Furthermore, concomitant treatment with zinc ameliorated HAART-induced penile oxidative stress and inflammation.
Conclusion
In conclusion, our present findings show that zinc improves sexual and erectile function in HAART-treated rats by upregulating erectogenic enzymes via the maintenance of penile redox balance.
... Neurotransmitter Dopamine (DA) which is highly conserved throughout evolution has been suggested to play an important role in normal sexual function (Hull et al., 2004;Andersson, 2011) and any disruption in the levels of DA leads to abnormal sexual behavior (Zahran et al., 2001;Shaltiel-Karyo et al., 2012). Studies have shown that DA in the hypothalamus plays a role in regulating sexual behaviors, however, the detailed mechanism of SD in PD is not known (Sakakibara et al., 2011). ...
Sexual dysfunction (SD) is one of the most common non-motor symptoms of Parkinson’s disease (PD) and remains the most neglected, under-reported, and under-recognized aspect of PD. Studies have shown that Dopamine (DA) in the hypothalamus plays a role in regulating sexual behavior. But the detailed mechanism of SD in PD is not known. Drosophila melanogaster shares several genes and signaling pathways with humans which makes it an ideal model for the study of a neurodegenerative disorder such as PD. Courtship behavior of Drosophila is one such behavior that is closely related to human sexual behavior and so plays an important role in understanding sexual behavior in diseased conditions as well. In the present study, a sporadic SD model of PD using Drosophila was developed and SD phenotype was observed based on abnormalities in courtship behavior markers. The Drosophila SD model was developed in such a way that at the window of neurotoxin paraquat (PQ) treatment [PQ is considered a crucial risk factor for PD due to its structural similarity with 1-methyl-4-phenyl pyridinium (MPP+), the active form of PD-inducing agent, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)], it does not exhibit mobility defects but shows SD. The whole brain tyrosine hydroxylase immunostaining showed no observable dopaminergic (DAergic) degeneration (number of DA neurons and fluorescence intensity of fluorescently labeled secondary antibodies that target anti-TH primary antibody) of the SD model. Similarly, there was no significant depletion of brain DA and its metabolite levels (HVA and DOPAC) as determined using HPLC-ECD (High-Performance Liquid Chromatography using Electrochemical Detector). The present study illustrates that the traits associated with courtship and sexual activity provide sensitive markers at the earlier stage of PD onset. This PQ-induced SD fly model throws an opportunity to decipher the molecular basis of SD under PD conditions and to screen nutraceuticals/potential therapeutic molecules to rescue SD phenotype and further to DAergic neuroprotection.
... In mammals and insects, there is a growing body of evidence that hormonal factors interact with biogenic amines and this functional interplay has been particularly described in the context of male reproduction. For example, testosterone is known to be essential for the display of male reproductive behavior by enhancing the processing of sexually relevant stimuli and this action has been shown to be driven through alterations in the synthesis, release and receptor expression for neurotransmitters such as dopamine (DA) and serotonin (Hull et al., 1999(Hull et al., , 2004. JH was found to be a critical signal in the emergence of DAmediated mating flight of A. mellifera drones by increasing simultaneously the expression levels of DA and D1-type dopamine receptor (Dop1) in the brain (Akasaka et al., 2010;Sasaki et al., 2012). ...
In insects, juvenile hormone (JH) is critical for the orchestration of male reproductive maturation. For instance, in the male moth, Agrotis ipsilon, the behavioral response and the neuronal sensitivity within the primary olfactory centers, the antennal lobes (ALs), to the female-emitted sex pheromone increase with fertility during adulthood and the coordination between these events is governed by JH. However, the molecular basis of JH action in the development of sexual behavior remains largely unknown. Here, we show that the expression of the paralogous JH receptors, Methoprene-tolerant 1 and 2 (Met1, Met2) and of the JH-inducible transcription factor, Krüppel homolog 1 (Kr-h1) within ALs raised from the third day of adult life and this dynamic is correlated with increased behavioral responsiveness to sex pheromone. Met1-, Met2- and Kr-h1-depleted sexually mature males exhibited altered sex pheromone-guided orientation flight. Moreover, injection of JH-II into young males enhanced the behavioral response to sex pheromone with increased AL Met1, Met2 and Kr-h1 mRNA levels. By contrast, JH deficiency suppressed the behavioral response to sex pheromone coupled with reduced AL Met1, Met2 and Kr-h1 mRNA levels in allatectomized old males and these inhibitions were compensated by an injection of JH-II in operated males. Our results demonstrated that JH acts through Met-Kr-h1 signaling pathway operating in ALs, to promote the pheromone information processing and consequently the display of sexual behavior in synchronization with fertility to optimize male reproductive fitness. Thus, this study provides insights into the molecular mechanisms underlying the hormonal regulation of reproductive behavior in insects.
... Increased cAMP levels, due to rapid cholesterol mobilization, are primarily responsible for an increase in steroid production by Leydig cells [45]. Therefore, increased levels of dopamine optimize hormone development, like testosterone, which contributes to improved sexual behavior [46,47]. Many bioactive constituents, including alkaloids, coumarins, flavonoids, and alkylamines, have been reported to be present in M. pruriens [48], which play a significant role in increasing the antioxidant potential in treated males. ...
Background and aim:
A significant cause of arsenic poisoning is polluted groundwater. Arsenic poisoning results in the suppression of spermatogenesis and the liver and kidneys are vulnerable to the toxic effects as well. Mucuna pruriens has been identified to have fertility-enhancing and anti-lipid peroxidation properties. Based on these properties of M. pruriens, this study aimed to investigate the efficacy of M. pruriens seed extract in reducing sodium arsenite-induced testicular impairment and hepato-renal histopathology in rats.
Materials and methods:
The study was divided into two groups; short-term (45 days) and long-term (90 days) treatment groups and each group was divided into nine subgroups. Subgroups 1 and 2 served as normal and N-acetyl cysteine (NAC) controls, respectively. Subgroups 3-9 received sodium arsenite in the drinking water (50 mg/L). Subgroup-4 received NAC (210 mg/kg body weight [BW]) orally once daily. Subgroups 5-7 received aqueous seed extract of M. pruriens (350, 530, and 700 mg/kg BW, respectively) orally once daily. Subgroups 8 and 9 received a combination of NAC and aqueous seed extract (350 and 530 mg/kg BW, respectively) orally once daily. Following the treatment, animals were sacrificed and sperm parameters and DNA damage were evaluated. Testis, liver, and kidneys were analyzed for histopathology.
Results:
Sodium arsenite-induced a significant reduction in sperm parameters and increase in the abnormal architecture of spermatozoa. Histology revealed tissue necrosis. The M. pruriens seed extract ameliorated the damaging effects of sodium arsenite with respect to tissue architecture and sperm parameters when coadministered.
Conclusion:
Mucuna pruriens has beneficial effects against the deleterious effects of sodium arsenite on various tissues. Thus, M. pruriens (530 and 700 mg/kg BW) supplementation would reduce the adverse changes observed with sodium arsenite exposure.
... Control group female offsprings Testosterone-exposed male offsprings Testosterone-exposed female offsprings brain, respectively (Hull et al., 2004;Lindamer et al., 1997). Because postnatal testosterone levels per se do not seem to vary between autistic and normal individuals, as previously mentioned, the enhancement of DA transmission by prenatal testosterone may be more meaningful than a direct influence of testosterone (Tordjman et al., 1995). ...
Background
A neurodevelopmental disease, autism spectrum disorder (ASD) occurs in males three times more commonly than girls. Higher prenatal testosterone exposure may result in autistic-like behaviour in boys, according to earlier research. It is unclear how fetal testosterone affects the development of autism. In this study, we tested the hypothesis that prenatal testosterone exposure in an animal model may result in autistic behaviors by modifying seratonin, dopamine, IGF-1, and oxytocin levels.
Materials and Methods
Group 1 (control, n = 6) and Group 2 (testosterone undecanoate, n = 6) of female rats were randomly assigned. For two to three days during the oestrus cycle, female rats were housed with a reproductive male (three females/one male). On the tenth day of gestation, rats in Group 1 received 1 ml/kg% 0.9 NaCl saline whereas rats in Group 2 received 250 mg/kg testosterone undecanoate. Until weaning on postnatal day 21 (P21), the mothers were permitted to care for their pups. On P21, 40 littermates—10 male and female for control, 10 male and female from mothers that exposed to testosterone—were arbitrarily split up and housed. On P50, these mature rats were tested for their behavior. The rats were then sacrificed. The brain tissue was subjected to histological examinations as well as biochemical tests for homovanillic acid (HVA), 5-Hydroxyindoleacetic acid (5-HIAA), oxytocin and Insulin-like growth factor-1 (IGF-1).
Results
The groups differed significantly in the behavioral examinations (three-chamber social test, passive avoidance learning analysis, open field test), with the testosterone-exposed groups exhibiting autistic symptoms to a higher extent. When compared to the control groups, testosterone exposure caused significant histological changes in the hippocampus CA1 and CA3 areas, including gliosis and cell death of neurons. In the testosterone-exposed groups, HVA, 5-HIAA and IGF-1 tissue expressions in the brain elevated whereas oxytocin levels reduced. These findings point to a potential connection between neurodevelopmental disorders like ASD and exposure to testosterone during gestation.
Conclusion
Overall, we revealed that prenatal testosterone exposure led to autistic traits by elevating seratonin, dopamine, and IGF-1 levels while lowering oxytocin levels.
The ability to evaluate valence of a social agent based on social experience is essential for an animal’s survival in its social group¹. Although hippocampal circuits have been implicated in distinguishing novel and familiar conspecifics2, 3, 4, 5, 6–7, it remains unclear how social valence is constructed on the basis of social history and what mechanisms underlie the heightened valence versatility in dynamic relationships. Here we demonstrate that the ventral (v)CA1 integrates serotonin (5-HT) inputs from the dorsal raphe and neurotensin inputs from the paraventricular nucleus of the thalamus (PVT) to determine positive or negative valence of conspecific representations. Specifically, during an appetitive social interaction 5-HT is released into the vCA1 and disinhibits pyramidal neurons through 5-HT1B receptors, whereas neurotensin is released during an aversive social interaction and potentiates vCA1 neurons directly through NTR1s. Optogenetic silencing of dorsal raphe 5-HT and PVT neurotensin inputs into the vCA1 impairs positive and negative social valence, respectively, and excitation flexibly switches valence assignment. These results show how aversive and rewarding social experiences are linked to conspecific identity through converging dorsal raphe 5-HT and PVT neurotensin signals in the vCA1 that instruct opposing valence, and represent a synaptic switch for flexible social valence computation.
Serotonin is involved in multiple diverse and complex biological processes. Selective serotonin reuptake inhibitors (SSRIs) are often used to test this, and fluoxetine, a commonly detected SSRI in aquatic ecosystems from pharmaceutical pollution, has been found to disrupt important behaviours and functions in organisms exposed to the antidepressant. Increased serotonin generally has an inhibitory effect on sexual behaviour and decreased serotonin has a facilitatory effect, however in the few existing studies on fish, either no effect or the opposite effect have been reported in females, with most studies focusing on male behaviour. The present research aims to examine the role of the serotonin pathway in female sexual receptivity in the cichlid fish Nyassachromis cf. microcephalus . The sexual dimorphism and lekking system of this species, where male-male competition is aggressive and female choice is important, make them an important and interesting evolutionary system. Serotonin levels were modulated using fluoxetine and after a three-week exposure to their respective treatments (control - 0µg/L, low ecologically relevant dose - 0.54µg/L, high dose - 5.4µg/L), female sexual receptivity to male courtship was measured in a simulated lek mating arena where multiple males were presented simultaneously. Sexual receptivity was inhibited in females exposed to a high dose of fluoxetine. This behaviour change due to a disruption of the serotonin pathway could affect sexual selection in the long term, and in the short term highlights the potential for pollution to affect aquatic life by directly altering mating behaviour.
Highlights
- Disrupting the serotonin pathway reduces sexual receptivity in female cichlid fish
- The inhibitory effect of fluoxetine on female receptivity is dose-dependent
- The serotonin pathway could be important in the evolution of male mating strategies
- SSRI pollution could cause behaviour changes that amplify freshwater biodiversity loss
Extremely aggressive behavior, as the special pattern, is rare in most species and characteristic as contestants severely injured or killed ending the combat. Current studies of extreme aggression are mainly from the perspectives of behavioral ecology and evolution, while lacked the aspects of molecular evolutionary biology. Here, a high-quality chromosome-level genome of the parasitoid Anastatus disparis was provided, which the males exhibit extreme mate-competition aggression. The integrated multiomics analysis highlighted that neurotransmitter dopamine overexpression, energy metabolism (especially from lipid) and antibacterial activity are likely major aspects of evolutionary formation and adaptation for extreme aggression in A. disparis. Conclusively, our study provided new perspectives for molecular evolutionary studies of extreme aggression as well as a valuable genomic resource in Hymenoptera.
Background
Testosterone plays a crucial role in regulating sexual behavior among non‐human primates, working primarily by increasing copulatory behavior and sexual motivation. In this study, we analyzed fecal testosterone levels in five adult male Tibetan macaques ( Macaca thibetana ) living freely in the Huangshan National Reserve in Anhui Province. The aim was to investigate the relationships between fecal testosterone levels and sexually motivated behaviors.
Methods
We collected a total of 426 fecal samples and observed approximately 453 h of focal sampling behavioral data. Sexually motivated behaviors were categorized as sexual chase, grimace, and sexual‐inspection.
Results
The results showed a positive correlation between sexually motivated behaviors and copulatory behavior. Furthermore, all the three sexually motivated behaviors, including sexual chase, grimace, and sexual‐inspection, were positively correlated with fecal testosterone levels.
Conclusion
Our results demonstrated positive correlations between sexually motivated behaviors and fecal testosterone in free‐ranging Tibetan macaques.
In mammals, males execute a stereotypical and organized sequence of sexual behaviours, such as mounting, intromission, and ejaculation, to successfully complete copulation. However, the neural mechanisms that govern the sequential transitions of male copulatory behaviours remain unclear. Here, we report that dopamine (DA) and acetylcholine (ACh) dynamics in the ventral shell of the nucleus accumbens (vsNAc) closely align with serial transitions of sexual behaviours in male mice. In particular, the vsNAc exhibits a unique pattern of 1.5—2.2 Hz dual ACh/DA rhythms that correspond to the pelvic thrust rhythm during intromission. The dual ACh/DA rhythms are generated locally by reciprocal regulation between ACh and DA signalling via nicotinic acetylcholine (nAChR) and dopamine D2 (D2R) receptors, respectively. Knockdown of choline acetyltransferase (ChAT) and D2R expression in the vsNAc diminishes intromission and ejaculation. We showed that ACh signalling promotes the initiation of intromission, whereas DA signalling sustains intromission by inhibiting the activities of D2R—expressing neurons in the vsNAc. Moreover, optogenetic activation of ChATvsNAc neurons during intromission slows down the DA rhythm, a specific activity signature that precedes ejaculation, and leads to immediate ejaculation. Taken together, dual ACh/DA dynamics in the vsNAc coordinate sequential transitions of male copulatory behaviours from intromission to ejaculation.
Introduction:
Schizophrenia is a psychotic disorder and one of the most severe and impactful mental illnesses. Sexual dysfunction is highly prevalent in patients with schizophrenia but remains underdiagnosed and undertreated. Sexual dysfunction is frequently attributed to antipsychotics which may reduce medication adherence, but negative symptoms can also reduce sexual drive.
Areas covered:
This review provides an overview of the current knowledge about sexual dysfunction in patients with schizophrenia. The authors first review the literature concerning the mechanisms of sexual dysfunction and explore the impact of antipsychotics on sexual function. Finally, they present the available non-pharmacological and pharmacological treatment strategies for sexual dysfunction in patients with schizophrenia.
Expert opinion:
Sexual dysfunction in patients with schizophrenia is still underrated by clinicians despite having a negative impact on the quality of life and therapeutic adherence. Antipsychotic treatment is still perceived as a major cause of sexual impairment. Psychiatrists must be aware of this condition and actively question the patients. A comprehensive approach, addressing pharmacological and non-pharmacological aspects, is fundamental for managing sexual dysfunction in schizophrenia. Pharmacological strategies include (1) Serum-level adjustment of the antipsychotic dose, if possible (2) switching to a well-tolerable antipsychotic (aripiprazole, brexpiprazole) and (3) adding a coadjuvant drug (phosphodiesterase-5 inhibitors).
Introduction
Sexual health, an integral component of overall well-being, is frequently compromised by common yet underdiagnosed sexual dysfunctions. Traditional interventions encompass pharmaceutical and psychological treatments. Unconventional therapies, like MDMA, offer hope for sexual dysfunction. This review delves into MDMA’s effects on sexual responsiveness and its potential role in treating sexual dysfunction.
Objectives
The purpose of this review is to elucidate effects of MDMA on different domains of the female and male sexual response cycles.
Methods
We conducted a systematic review on the effects of MDMA on each domain of the female and male sexual response cycles. PubMed, MEDLINE, and EMBASE were queried, and results were screened using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Search terms utilized were “MDMA” or “ecstasy” in combination with “desire,” “arousal,” “lubrication,” “orgasm,” “pleasure,” “libido,” “erection,” and “ejaculation.” Inclusion criteria for this review were MDMA use by study subjects and sexual outcomes in at least 1 domain of the female and/or male sexual response cycles were described and measured. Randomized controlled trials, cohort studies (both prospective and retrospective), surveys, and literature reviews published between January 2000 and June 2022 were included. Case reports and studies that did not address conditions of interest were excluded from analysis. Duplicated search results were screened out. The remaining studies were then read in full text to ensure they met inclusion and exclusion criteria for analysis.
Results
We identified 181 studies, of which 6 met criteria for assessment of the female sexual response cycle and 8 met criteria for assessment of the male sexual response cycle. Four of 6 studies reported increased sexual desire with MDMA use among women. Arousal and lubrication were improved with MDMA use in 3 of 4 studies, but they were not affected in 1 randomized control study. In men, 7 studies evaluated the effects of MDMA on desire and/or arousal, 5 studies measured impact on erection, 3 on orgasm, and 2 on ejaculation. Sixty percent of interview-based studies reported increased sexual desire in men, while 40% reported mixed or no effect. Two studies reported impairment of erection, 2 reported mixed effects, and 1 reported fear of erection impairment. In both men and women, all studies evaluating orgasm reported delay in achieving orgasm but increased intensity and pleasure if achieved. Primary outcome measures were variable and largely qualitative.
Conclusion
Our findings suggest that MDMA generally increases sexual desire and intensifies orgasm when achieved. While producing conflicting evidence on sexual arousal in both sexes, MDMA may impair erectile and ejaculatory function in men.
Tryptophan hydroxylase 1 (TPH1) has emerged as a target for the treatment of metabolic diseases including obesity and fatty liver disease. A series of xanthine derivatives were synthesized and evaluated for their TPH1 inhibition. Among the synthesized compounds, compound 40 showed good in vitro activity and liver microsomal stability. Docking studies revealed that compound 40 showed better binding to TPH1 via key intermolecular interactions involving the xanthine scaffold, imidazo-thiazolyl ring, and hydroxyl-containing phenacyl moiety. In addition, compound 40 effectively suppressed the adipocyte differentiation of 3T3-L1 cells.
Why do people fall in love? Does passion fade with time? What makes for a happy, healthy relationship? This introduction to relationship science follows the lifecycle of a relationship – from attraction and initiation, to the hard work of relationship maintenance, to dissolution and ways to strengthen a relationship. Designed for advanced undergraduates studying psychology, communication or family studies, this textbook presents a fresh, diversity-infused approach to relationship science. It includes real-world examples and critical-thinking questions, callout boxes that challenge students to make connections, and researcher interviews that showcase the many career paths of relationship scientists. Article Spotlights reveal cutting-edge methods, while Diversity and Inclusion boxes celebrate the variety found in human love and connection. Throughout the book, students see the application of theory and come to recognize universal themes in relationships as well as the nuances of many findings. Instructors can access lecture slides, an instructor manual, and test banks.
Inhibitors of enzymes that inactivate amine neurotransmitters (dopamine, serotonin), such as catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO), are thought to increase neurotransmitter levels and are widely used to treat Parkinson's disease and psychiatric disorders, yet the role of these enzymes in regulating behavior remains unclear. Here, we investigated the genetic loss of a similar enzyme in the model organism Drosophila melanogaster. Because the enzyme Ebony modifies and inactivates amine neurotransmitters, its loss is assumed to increase neurotransmitter levels, increasing behaviors such as aggression and courtship and decreasing sleep. Indeed, ebony mutants have been described since 1960 as "aggressive mutants," though this behavior has not been quantified. Using automated machine learning-based analyses, we quantitatively confirmed that ebony mutants exhibited increased aggressive behaviors such as boxing but also decreased courtship behaviors and increased sleep. Through tissue-specific knockdown, we found that ebony’s role in these behaviors was specific to glia. Unexpectedly, direct measurement of amine neurotransmitters in ebony brains revealed that their levels were not increased but reduced. Thus, increased aggression is the anomalous behavior for this neurotransmitter profile. We further found that ebony mutants exhibited increased aggression only when fighting each other, not when fighting wild-type controls. Moreover, fights between ebony mutants were less likely to end with a clear winner than fights between controls or fights between ebony mutants and controls. In ebony vs. control fights, ebony mutants were more likely to win. Together, these results suggest that ebony mutants exhibit prolonged aggressive behavior only in a specific context, with an equally dominant opponent.
This chapter examines the relationship between acute exercise and physiological sexual arousal in women. The first section of the chapter provides foundational knowledge on the physiological sexual arousal response, which is characterized by increased blood flow to the genitals and subsequent vasocongestion, and then highlights the faciliatory effect of acute exercise on this response. Based on a series of studies that investigated autonomic nervous system influences on sexual arousal in women, the second section suggests that activation of the sympathetic nervous system is most likely the mechanism that facilitates the relationship between acute exercise and increased physiological sexual arousal. Finally, the chapter discusses key clinical implications of the relationship between acute exercise and physiological arousal, particularly for women who have a history of childhood sexual abuse, women who have undergone hysterectomies, and women who report sexual arousal problems due to antidepressant medication use.KeywordsFemale sexual functionSexual arousalAcute exerciseSympathetic nervous system
Resultados de comparaciones reportadas entre países alrededor del globo desde 1999 indican quela riqueza de las naciones crece consistentemente con la distancia a la línea ecuatorial. ¿Está el territorio peruano exento de esta tendencia? Para reconciliar la contradictoria evidencia nacional y entender el rol de ciertos factores geofísicos y sociales, este estudio utilizó coordenadas GPS, datos de cuestionarios, archivos de clima, e información censal existentes en varias bases de datos(Encuesta Demográfica y de Salud Perú 2000, Climate Wizard, G-Econ). Los activos del hogar crecen de norte a sur en las regiones ecológicas de Brack de orientación latitudinal estudiadas (desierto, puna, yunga, Amazonía), especialmente en ámbitos rurales, y la educación de la mujer lo hace en las tres primeras. Ni la temperatura ni otras 14 variables geofísicas y sociales dan cuenta de los efectos, aunque el poder doméstico de la mujer los explica en la ecoregión Yunga. Los resultados pueden entenderse en dos perspectivas teóricas. Una, acorde con las tesis evolucionistas de Lynn, Rushton y Kanazawa, sugiere la fijación genética de niveles intelectuales diferenciales producidos por una adaptación ancestral de los peruanos a distintas condicionesde clima y altura. La otra, combinando lo que se conoce sobre radiación ultravioleta, vitamina D, y producción de hormonas sexuales con la teoría de la confluencia de Zajonc, se define por la tasa de fertilidad y consecuente ambiente intelectual hogareño para el niño. Ambas predicen el incremento del cociente intelectual y los puntajes educativos PISA del norte al sur peruanos, pero de una se desprende la educación y de la otra la planificación familiar como estrategias promotoras de desarrollo humano.
Background:
Although many studies reported the neuropsychiatric involvement of testosterone (T) levels in the development of mood disorders, its role in this disabling disorder is still not well understood. Therefore, in this review, we aim to summarize the current literature exploring serum testosterone levels in both major depressive disorder (MDD) and bipolar disorder (BD), with particular attention given to the possible causal relationship between pathological mood alteration and T levels.
Methods:
We selected 9 original studies from a bibliographic search on PubMed, excluding studies on hormonal therapy and other psychiatric disorders other than mood disorders.
Results:
The results reported by the reviewed studies were conflicting especially with regards to the presence of dysfunctional levels of T in patients with BD. Specifically, while MDD was found to be associated with low levels of T compared to healthy controls (HC), in BD the results were highly heterogeneous, with a mixed picture of reduced, increased or no difference in T levels in BD patients compared to HC.
Limitations:
Studies were highly heterogeneous in terms of samples employed, psychometric scales used for assessing depressive symptoms, T assay methods and therapeutic regimens.
Conclusions:
Overall, T levels were shown to be reduced in both MDD and BD patients. However, T levels seem to have a different pattern in suicidal BD women, which showed higher T levels, ultimately suggesting an association with self-harming behaviors. Nonetheless, taken together, these findings suggest that T could be useful as a biomarker in mood disorders and provide guidance for future research.
Locomotor performance is an indicator of dynamic exercise; thus, it is a central trait in many animal behaviours. Although higher locomotor endurance may increase male reproductive success (e.g., in mate searching and male-male contests), investment in other male reproductive traits (e.g., male attractiveness and sperm competition) may be decreased through energy consumption due to higher activity levels. Here, I investigated male attractiveness, mating success, and paternity success using males of the red flour beetle Tribolium castaneum selected for higher (H) and lower (L) locomotor endurance. Although there was no difference in male attractiveness between the selection regimes, H males had significantly higher mating success than L males. Conversely, L males had significantly higher paternity success than H males. Therefore, there was a trade-off between mating success and paternity success among the selection regimes, suggesting that locomotor endurance affects male reproduction in T. castaneum, and individual variation of locomotor endurance may be maintained within a population.
Male animals exhibit positive and negative infant-directed behaviors, yet the underlying neural mechanisms remain unknown. The amygdalohippocampal area (AHi) regulates social behavior through neural projections to multiple brain regions. Although AHi neurons that project to the medial preoptic area (MPOA) were reported to promote infanticide in male mice, MPOA-projecting AHi neurons are activated by both parenting and infanticide, suggesting heterogeneity within these neurons. Here using a newly developed, virus-mediated projection-specific and activity-dependent cell labeling method (vPAL), we uncovered two distinct functional, electrophysiological, and transcriptional populations in MPOA-projecting AHi neurons, designated infanticide-related and parenting-related neurons. Furthermore, activation of serotonin receptor 7, which is highly expressed in parenting neurons, selectively suppressed infanticide while promoting parenting in virgin male mice. This study provides a better understanding of the neuronal populations, functions, and properties that previous labeling methods masked.
Background
Infertility affects 15% of all couples worldwide. According to recent research, 50% of cases of infertility are solely due to male factors. A decrease in motility is directly related to infertility. The purpose of this study was to see how sperm motility was affected by the combination of serotonin (5-HT), selenium (Se), zinc (Zn), vitamin D, and vitamin E supplementation.
Methods and results
Semen samples were incubated for 75 minutes at 37°C in media containing varying concentrations of 5-HT, Se, Zn, vitamin D, and E. Sperm concentration and motility were assessed at the end of the incubation. Calculations were made for each supplement to determine the proportions of fast progressive (+ 4), slow progressive (+ 3), non-progressive (+ 2), and immotile (+ 1) sperm cells. There was a significant improvement in fast progressive motility when compared to the control groups. 5-HT (200 µM), Se (2 µg), Zn (10 µg), vitamin D (100 nM), and vitamin E (2 mmol) concentrations have also been shown to increase fast progressive sperm motility. Three different mixtures were tested for their effects on sperm motility, and the one with the highest serotonin content was also found to have higher sperm motility than the others. While the mean + 4 sperm motility in the control group was 5.26%, it increased to 16.45% in the first mixture.
Conclusion
Sperm motility is improved by incubating with 5-HT, Se, Zn, Vitamin D, and E. These molecules may enhance the success of assisted reproduction techniques when present in sperm preparation media.
Sexual experience facilitates subsequent male sexual behavior; activation of the N-methyl-D-aspartate (NMDA) glutamate receptor may play a role in this experience-induced enhancement. In this article, the authors report that systemic injections of MK-801, an NMDA receptor antagonist, impaired male sexual behavior in sexually naive and sexually experienced male rats. Furthermore, saline-treated rats that received 7 daily exposures to an inaccessible estrous female instead of sexual experience displayed enhancement of copulation on the following day. Injections of MK-801 before each of these exposures inhibited the experience-induced enhancement on the drug-free test on Day 8. These data suggest that stimulation of NMDA receptors enhances sexual performance immediately and mediates the experience-induced enhancement of subsequent copulatory behavior.
The effects of dopaminergic and opioidergic drugs on sexual incentive motivation were evaluated in sexually inexperienced male rats subjected to a choice procedure. Various parameters of ambulatory activity were recorded as well. Two drugs stimulating dopaminergic neurotransmission, amphetamine and apomorphine, failed to affect sexual incentive motivation, although ambulatory activity was enhanced by amphetamine. The dopamine antagonist cis(Z)-flupenthixol reduced sexual incentive motivation, but only at a dose that severely disrupted motor function. Morphine had marginal effects on sexual motivation but reduced ambulatory activity. These effects were not reduced by a peripheral opioid antagonist, methylnaloxone. Loperamide, a peripheral opioid agonist, reduced sexual motivation through an opioid-independent action. Naloxone was ineffective. Neither dopamine nor opioids seem to be important for sexual incentive motivation.
Extracellular concentrations of dopamine (DA) and its metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were examined concurrently, using in vivo microdialysis, in the nucleus accumbens and dorsal striatum of sexually active male rats during tests of locomotor activity, exposure to a novel chamber, exposure to sex odors, the presentation of a sexually receptive female, and copulation. DA increased significantly in the nucleus accumbens when the males were presented with a sexually receptive female behind a screen and increased further during copulation. Although DA also increased significantly in the dorsal striatum during copulation, the magnitude of the effect was significantly lower than that observed in the nucleus accumbens. In contrast, forced locomotion on a rotating drum, exposure to a novel chamber, and exposure to sex odors did not increase DA significantly in either region, although both DOPAC and HVA increased significantly in both regions during the locomotion test. These results indicate that novelty or locomotor activity alone cannot account for the increased extracellular DA concentrations observed in the nucleus accumbens of male rats during the presentation of a sexually receptive female behind a screen, nor can they account for the increased DA concentrations observed in both the nucleus accumbens and dorsal striatum of male rats during copulation. The preferential increase in DA transmission in the nucleus accumbens, compared with that in the striatum, suggests that anticipatory and consummatory aspects of sexual activity may belong to a class of naturally occurring events with reward values that are mediated by DA release in the nucleus accumbens.
Serotonin (5-HT) is generally inhibitory to masculine sexual behavior. It has been suggested that 5-HT released after ejaculation may promote the sexual quiescence of the postejaculatory interval (PEI). The following experiments were conducted to test (1) whether extracellular 5-HT increases in either the anterior lateral hypothalamic area (LHA A ) or the medial preoptic area (MPOA) of male rats after ejaculation; (2) whether increasing 5-HT in these sites, by microinjecting the selective serotonin reuptake inhibitor alaproclate, could inhibit copulatory abilities; and (3) whether copulation deficits produced by alaproclate were attributable to locomotor impairments. The effects of local application of alaproclate on extracellular 5-HT levels in the LHA A and the MPOA were also tested. Extracellular serotonin was measured in all experiments using in vivo microdialysis.
Ejaculation was correlated with enhanced 5-HT release from the LHA A ; no 5-HT increases were observed before ejaculation, and levels were decreased toward basal values during a subsequent copulatory series. Elevating 5-HT in the LHA A by microinjecting alaproclate inhibited copulation by increasing the latency to mount, intromit, and ejaculate. This inhibition did not result from nonspecific locomotor impairments. In the MPOA, 5-HT release remained stable throughout copulation, and microinjecting alaproclate into this site did not significantly alter sexual behavior.
These data support the large body of evidence suggesting that 5-HT is inhibitory to masculine sexual behavior. Furthermore, the LHA A , but not the MPOA, may be one site responsible for serotonergic inhibition of copulation during the PEI.
Dopamine (DA) activity in the medial preoptic area (MPOA) contributes to the control of male rat sexual behavior. We tested (1) whether extracellular DA increases during precopulatory exposure to an estrous female and during copulation, (2) whether exposure to another male increases extracellular DA, (3) whether motor activity during copulation accounts for increased DA levels, and (4) whether concurrent or recent testosterone influences DA levels or copulation in castrates. Extracellular DA and its metabolites in male rats' MPOA were measured using microdialysis. DA level increased during precopulatory exposure to the female in all animals that subsequently copulated; this included all intact animals, all testosterone-treated castrates, and 9 of 14 1- week castrates treated with oil vehicle. DA levels did not increase in any animal that subsequently failed to copulate, including the remaining 1-week, and all 2-week, vehicle-treated castrates. When the barrier was removed and the animals were allowed to copulate, levels of DA and its metabolites continued to rise in intact males and in castrates that copulated. The DA response to the estrous female could not be attributed to nonsexual social stimuli, since exposure to another male was ineffective. The DA response to copulation could not be attributed primarily to motor activity, since animals running voluntarily in a running wheel did not show significantly increased DA. These and previous data suggest that DA released in the MPOA in response to an estrous female may contribute to sexual motivation and copulatory proficiency. Testosterone may promote copulation in part through permissive actions on dopamine release.
The ability of dopamine (DA) receptor antagonists to disrupt anticipatory and consummatory measures of sexual behavior displayed by male rats in bilevel chambers was investigated. In Experiment 1, systemic administration of haloperidol, pimozide, and the D1 antagonist SCH 23390 reduced the number of anticipatory level changes (LC) displayed during a 5-min period before the introduction of a sexually receptive female, increased the mount and intromission latencies (ML and IL), and decreased the number of intromissions before ejaculation (NI) and the total number of ejaculations (NE). The dosages of these drugs required to reduce the LC were lower than those required to increase the ML or IL. Clozapine and the D2 antagonist sulpiride reduced the LC and increased the IL at comparable dosages, although neither drug affected the NI or NE. High dosages of haloperidol, pimozide, and clozapine delayed or abolished level changing and the initiation of copulation. In Experiment 2, bilateral infusions of haloperidol into the nucleus accumbens reduced the LC but did not affect consummatory measures of copulation, whereas bilateral infusions into the dorsal striatum increased the NE. Midline infusions of haloperidol to the medial preoptic area (MPOA) produced nearly all the effects of systemic administration, including a reduced LC, increased ML and IL, a decreased NI, and a decreased NE. These results indicate that both anticipatory and consummatory measures of sexual behavior were disrupted by DA receptor antagonists; however, the measure of anticipatory sexual behavior was more sensitive to disruption than consummatory measures of copulation. DA in the nucleus accumbens and MPOA may be involved in the control of anticipatory sexual behavior, whereas in the MPOA it may also be involved in the initiation of copulation and copulatory rate.
The D1/D2 dopamine agonist apomorphine, microinjected into the medial preoptic area (MPOA), facilitates male rat sexual behavior and the D1/D2 antagonist cis-fiupenthixol in the MPOA impairs it. The present study investigated the roles of Dl and D2 receptors in the regulation of copulation by microinjecting drugs selective for these receptors into the MPOA. The D2 agonist LY- 163502delayedthe onset and slowed the rate of copulation and also reduced the number of vaginal intromissions required to trigger ejaculation (reduced ejaculatory threshold). The Dl ago- fist SKF-82526 had no effect, either alone or together with LY- 163502. The Dl antagonist SCH-23390 delayed the onset of copulation and decreased ejaculatory threshold, as had the D2 agonist. A low dose of the D2 agonist alone and together with the Dl antagonist delayed the onset of copulation and reduced ejaculatory threshold; the combination of drugs was more effec- tive than LY-1 63502 alone. Only the combination of drugs slowed the rate of copulation and delayed the resumption of copulation after an ejaculation. Thus, increasing the D2/D1 ratio in the MPOA, by selective stimulation of D2 and/or antagonism of Dl receptors, delays the onset of copulation and reduces ejaculatory threshold, possibly by altering autonomic control of penile re- flexes.
Studies addressing behavioral functions of dopamine (DA) in the nucleus accumbens septi (NAS) are reviewed. A role of NAS DA in reward has long been suggested. However, some investigators have questioned the role of NAS DA in rewarding effects because of its role in aversive contexts. As findings supporting the role of NAS DA in mediating aversively motivated behaviors accumulate, it is necessary to accommodate such data for understanding the role of NAS DA in behavior. The aim of the present paper is to provide a unifying interpretation that can account for the functions of NAS DA in a variety of behavioral contexts: (1) its role in appetitive behavioral arousal, (2) its role as a facilitator as well as an inducer of reward processes, and (3) its presently undefined role in aversive contexts. The present analysis suggests that NAS DA plays an important role in sensorimotor integrations that facilitate flexible approach responses. Flexible approach responses are contrasted with fixed instrumental approach responses (habits), which may involve the nigro-striatal DA system more than the meso-accumbens DA system. Functional properties of NAS DA transmission are considered in two stages: unconditioned behavioral invigoration effects and incentive learning effects. (1) When organisms are presented with salient stimuli (e.g., novel stimuli and incentive stimuli), NAS DA is released and invigorates flexible approach responses (invigoration effects). (2) When proximal exteroceptive receptors are stimulated by unconditioned stimuli, NAS DA is released and enables stimulus representations to acquire incentive properties within specific environmental context. It is important to make a distinction that NAS DA is a critical component for the conditional formation of incentive representations but not the retrieval of incentive stimuli or behavioral expressions based on over-learned incentive responses (i.e., habits). Nor is NAS DA essential for the cognitive perception of environmental stimuli. Therefore, even without normal NAS DA transmission, the habit response system still allows animals to perform instrumental responses given that the tasks take place in fixed environment. Such a role of NAS DA as an incentive-property constructor is not limited to appetitive contexts but also aversive contexts. This dual action of NAS DA in invigoration and incentive learning may explain the rewarding effects of NAS DA as well as other effects of NAS DA in a variety of contexts including avoidance and unconditioned/conditioned increases in open-field locomotor activity. Particularly, the present hypothesis offers the following interpretation for the finding that both conditioned and unconditioned aversive stimuli stimulate DA release in the NAS: NAS DA invigorates approach responses toward `safety'. Moreover, NAS DA modulates incentive properties of the environment so that organisms emit approach responses toward `safety' (i.e., avoidance responses) when animals later encounter similar environmental contexts. There may be no obligatory relationship between NAS DA release and positive subjective effects, even though these systems probably interact with other brain systems which can mediate such effects. The present conceptual framework may be valuable in understanding the dynamic interplay of NAS DA neurochemistry and behavior, both normal and pathophysiological.
Neurobiological Effects of Sex Steroid Hormones describes the neurobiological basis for the understanding of how sex steroid hormones, oestrogen and testosterone, interact with parts of the brain. The contributors have all made significant advances in the understanding of how these steroids regulate neural function, and how this activity is translated into reproductive behaviours necessary for the propagation of the species. This book covers a broad range of topics, extending from the molecular and cellular processes, through the action of steroids on neurotransmission, all the way to defining the brain circuitry involved in both male and female behaviour. This volume presents a snapshot of the rapidly advancing field of reproductive neuroendocrinology by the investigators who are most intimately involved with the discoveries.
Neurobiological Effects of Sex Steroid Hormones describes the neurobiological basis for the understanding of how sex steroid hormones, oestrogen and testosterone, interact with parts of the brain. The contributors have all made significant advances in the understanding of how these steroids regulate neural function, and how this activity is translated into reproductive behaviours necessary for the propagation of the species. This book covers a broad range of topics, extending from the molecular and cellular processes, through the action of steroids on neurotransmission, all the way to defining the brain circuitry involved in both male and female behaviour. This volume presents a snapshot of the rapidly advancing field of reproductive neuroendocrinology by the investigators who are most intimately involved with the discoveries.
Several lines of evidence suggest that nitric oxide (NO) is involved in the neuroendocrine control of reproductive function. This study was undertaken to determine 1) NO activity in the medial preoptic area (MPOA) where LHRH- and NO synthase-containing neurons are coextensive; 2) whether N-methyl-D-aspartate (NMDA) receptor activation, which stimulates LHRH release, augments NO activity in the MPOA; and 3) whether NO activation in the MPOA underlies the steroid dependency of NMDA-induced pituitary LH release. As extracellular levels of cGMP in discrete brain sites are a reliable index of basal and stimulated activity of NO, extracellular cGMP levels in the MPOA of freely moving, awake rats were measured by microdialysis in the current study. In the first experiment, the MPOA of intact and castrated male rats were microdialyzed with artificial cerebrospinal fluid at a rate of 5 microliters/min. The basal level of cGMP efflux was determined from the initial seven samples collected at 20-min intervals. The N...
In the male Syrian hamster, mating is dependent on chemosensory and hormonal stimuli, and interruption of either input prevents copulation. The medial amygdaloid nucleus (Me) is a key nodal point in the neural circuitry controlling male sexual behavior because it relays both odor and steroid cues. Me is comprised of two major subdivisions, anterior (MeA) and posterior (MeP), which have distinct, although overlapping efferent projections. The present study investigated the afferents and efferents of MeA and MeP by using combined anterograde and retrograde tract tracing. Phaseolus vulgaris-leucoagglutinin and cholera toxin B were injected by iontophoresis through a single glass micropipette and detected by immunohistochemistry. MeA has widespread connections with olfactory structures, whereas MeP is heavily interconnected with steroid-responsive brain regions. The efferent projections of MeA and MeP were similar to those reported previously for the rat and hamster. In particular, MeP projects to the posteromedial subdivision of the bed nucleus of the stria terminalis (BNST) and to the medial preoptic nucleus, whereas MeA projects to adjacent subnuclei in BNST and the preoptic area. MeA and MeP also have distinct patterns of afferent input. Furthermore, the combination of anterograde and retrograde tract tracers shows that MeA and MeP are each bidirectionally connected with each other and with limbic nuclei. These results demonstrate that subnuclei of Me are interconnected with limbic structures in hamster brain. These connections may contribute to chemosensory and hormonal integration to control male sexual behavior. J. Comp. Neurol. 399:189-209, 1998. (C) 1998 Wiley-Liss, Inc.
This chapter summarizes the progress made in understanding how hormones, the central nervous system, and the periphery interact to regulate male sexual behavior, focusing on how that understanding developed, and where it is incomplete. It summarizes recent research on the neural mechanisms by which males integrate hormonal and sensory inputs to produce adaptive behavioral and physiological responses, not only in the context of mating, but also in other contexts. It describes the copulatory behaviors of species commonly studied in the laboratory, the paradigms and measures used to study them, and the conceptual contexts in which the research takes place. It also reviews the behavioral effects of gonadal steroids, and systemically or intraventricularly administered drugs. It summarizes the information about the functions of the brain areas implicated in the control of male sexual behavior, including effects of lesions and stimulation, local hormonal and pharmacological manipulations, and measures of neural activity. Further, it describes the interconnections among the neural structures that mediate sexual behavior.
The medial preoptic area (MPOA) is an important integrative site for male sexual behavior. Dopamine (DA) is released in the MPOA of male rats shortly before and during copulation. The recent presence of testosterone (T) may be necessary for this precopulatory increase in release. Previously, the postcastration loss of copulatory ability mirrored the loss of the DA response to an estrous female, and the restoration of copulation with exogenous T was concurrent with the reemergence of this DA response. The present study investigated the effectiveness of the two major metabolites of T in maintaining copulation and basal and female-stimulated DA levels. Adult male rats were castrated and received daily injections of estradiol benzoate (EB), dihydrotestosterone benzoate (DHTB), EB + DHTB, testosterone propionate (TP), or oil vehicle for 3 weeks. Microdialysis samples were collected from the MPOA during baseline conditions, exposure to an estrous female behind a barrier, and copulation testing. EB + DHTB- and TP-treated animals had normal basal DA levels and showed a precopulatory DA response, and most copulated normally. EB-treated castrates had high basal DA levels, but failed to show a female-stimulated increase; most intromitted, but none ejaculated. DHTB- and oil-treated groups had low basal levels of extracellular DA that did not increase during copulation testing; most failed to mount and none ejaculated. These results suggest that E maintains normal basal levels of extracellular DA in the MPOA, which are sufficient for suboptimal copulation, but that androgen is required for the female-stimulated increase in DA release and for facilitation of ejaculation.
Sexual problems are highly prevalent in both men and women and are affected by, among other factors, mood state, interpersonal functioning, and psychotropic medications.The incidence of antidepressant-induced sexual dysfunction is difficult to estimate because of the potentially confounding effects of the illness itself, social and interpersonal comorbidities, medication effects, and design and assessment problems in most studies. Estimates of sexual dysfunction vary from a small percentage to more than 80%. This article reviews current evidence regarding sexual side effects of selective serotonin reuptake inhibitors (SSRIs). Among the sexual side effects most commonly associated with SSRIs are delayed ejaculation and absent or delayed orgasm. Sexual desire (libido) and arousal difficulties are also frequently reported, although the specific association of these disorders to SSRI use has not been consistently shown. The effects of SSRIs on sexual functioning seem strongly dose-related and may vary among the group according to serotonin and dopamine reuptake mechanisms, induction of prolactin release, anticholinergic effects, inhibition of nitric oxide synthetase, and propensity for accumulation over time. A variety of strategies have been reported in the management of SSRI-induced sexual dysfunction, including waiting for tolerance to develop, dosage reduction, drug holidays, substitution of another antidepressant drug, and various augmentation strategies with 5-hydroxytryptamine-2 (5-HT2), 5-HT3, and [small alpha, Greek]2 adrenergic receptor antagonists, 5-HT1A and dopamine receptor agonists, and phosphodiesterase (PDE5) enzyme inhibitors. Sexual side effects of SSRIs should not be viewed as entirely negative; some studies have shown improved control of premature ejaculation in men. The impacts of sexual side effects of SSRIs on treatment compliance and on patients' quality of life are important clinical considerations. (J Clin Psychopharmacol 1999;19:67-85)
Previous studies have shown that gonadectomy in adult male rats induces a complex series of region- and time-specific changes in the density of presumed cerebral cortical dopamine axons that are immunoreactive for tyrosine hydroxylase. The present study asked whether noradrenergic cortical afferents also show hormone sensitivity by assaying axons immunoreactive for the enzyme dopamine-β-hydroxylase in representative areas of acutely and chronically gonadectomized and sham-operated adult male rats. Catecholamine afferents (both tyrosine hydroxylase-immunoreactive and dopamine-β-hydroxylase-immunoreactive) were also quantified in gonadectomized rats supplemented with testosterone propionate, with 17-β-estradiol, or with 5-α-dihydrotestosterone. Analyses of noradrenergic (dopamine-β-hydroxylase) afferents revealed no differences in axon appearance or density among the hormonally intact and hormonally manipulated groups. However, analyses of tyrosine hydroxylase immunoreactivity revealed an unexpected division of labor among ovarian and testicular hormones in ameliorating the effects of acute verses chronic hormone deprivation on these afferents. Estradiol replacement attenuated the decreases in immunoreactivity induced by acute gonadectomy, but was ineffective in suppressing changes in immunoreactivity stimulated by chronic gonadectomy. In contrast, supplementing gonadectomized animals with dihydrotestosterone provided no protection from acute decreases in innervation, but fully attenuated both the supragranular decreases and infragranular increases in tyrosine hydroxylase-immunoreactive axon density that mark the association cortices of chronically gonadectomized rats. Together these findings indicate both long- and short-term effects of gonadectomy on cortical catecholamines, principally target dopamine afferents, and that chronic gonadectomy, which selectively disturbs dopamine innervation in the prefrontal cortices, involves a compromise in androgen signaling pathways. J. Comp. Neurol. 427:617–633, 2000. © 2000 Wiley-Liss, Inc.
The mesocorticolimbic dopamine tract is considered to be a substrate for motivation and reward as well as for locomotor behavior. The present experiments assessed the role of dopamine cell bodies in the ventral tegmental area (VTA), the source of this tract, in the copulatory behavior of male rats. The dopamine agonist apomorphine or the dopamine antagonistcis-flupenthixol were microinjected into the VTA immediately before sexual behavior tests with a receptive female. Apomorphine delayed the onset of copulation and slowed its rate, presumably by stimulating somatodendritic autoreceptors and thereby decreasing the firing rate of VTA neurons. Control injections of apomorphine into the substantia nigra were without effect.cis-Flupenthixol, which would have blocked autoreceptors and thereby depolarized VTA neurons, shortened the latency to begin copulating in those animals that did copulate; however, fewer animals exhibited sexual behavior. One possible explanation for the apparently contradictory effects ofcis-flupenthixol may be that VTA neurons increased their rate of firing in some animals leading to a faster onset of copulation, but that in other animals depolarization block in a substantial number of neurons resulted in a lack of copulation. These results are consistent with a contribution of the mesocorticolimbic dopamine tract to motivational and/or motor aspects of male copulatory behavior.
This report presents evidence of changes in the concentration of monoamine neurotransmitters and their metabolites in homogenates of spinal cord and brain areas of male rats related to specific events of their mating behavior. Intact male rats were allowed to copulate with receptive females and decapitated immediately after either the first intromission or the first ejaculation. Non-mating control animals were exposed to other males, instead of females. The concentration of monoamines (norepinephrine, dopamine and serotonin) and some of their major metabolites (DOPAC and HIAA) in homogenates of discrete brain areas (parietal cortex, preoptic region, mediobasal hypothalamus) and lumbosacral spinal cord were measured by HPLC-ED. Results suggest that sexual arousal is associated with both increased dopaminergic activity in the preoptic region and inhibition of descending monoaminergic signals to the lumbosacral cord, whereas ejaculation is accompanied by increased activity of the serotonergic, as well as dopaminergic, innervation of the preoptic region. These findings give neurochemical support to notions of central monoamines involvement in sexual behavior suggested by previous pharmacological studies.
Manipulations of dopamine levels in the dorsal and ventral striatum are shown to affect the activation of behaviour in distinct, yet parallel ways, which depend upon the nature of the neocortical and limbic input to these structures. Whereas dopamine in the dorsal striatum contributes to the sensorimotor co-ordination of consummatory behaviour and the development of a ‘response set’ in motor preparatory processes for skilled responses, dopamine in the ventral striatum influences the impact of reward-related stimuli on appetitive aspects of behaviour. The circumstances under which the striatal dopamine projections are normally active to effect these functions are defined by studies which attempt to correlate firing in single units or neurochemical indices of dopamine activity with environmental conditions, internal states and behaviour.
The role of dopaminergic transmission in the incentive–motivational processes involved in the generation of male sexual behavior was examined. Three groups of sexually naı̈ve Long–Evans male rats traversed a straight alley for one of three goalbox targets: an empty goalbox, a nonestrous female, or an estrous female. A Plexiglas partition within the goalbox allowed for the perception of visual, auditory, and olfactory cues, but prevented physical contact. Baseline run times revealed that subjects returned to the goalbox significantly faster for an estrous female than for a nonestrous female, replicating our earlier work on the inherent incentive value of primary female cues. When subjects were then pretreated with the dopamine receptor antagonist, haloperidol (0.0, 0.075, or 0.15 mg/kg), they expressed decreased sexual motivation as reflected by increased run times for estrous female targets. Subjects' run times for the empty goalbox condition were unaffected by haloperidol, suggesting that the drug did not reliably impair motoric capacity. Results support the contention that central dopaminergic systems are involved in the regulation of the positive, unconditioned incentive value of estrous female cues.
In the present experiments we extend previous findings that established a relationship between feeding behavior and hypothalamic serotonin as measured by in vivo microdialysis. The new result is hypothalamic release of serotonin in anticipation of eating when the animal sees and smells food. We have now verified brain serotonin peaks in four different ways: 1.1) a serotonergic reuptake blocker (fluoxetine 1 or 10 μM) in the perfusion medium raised basal levels of serotonin.2.2) every sample was oxidized at two potentials using a dual potentiostat to confirm the voltage characteristics of each peak.3.3) serotonin peaks were reduced by the selective serotonin cell body agonist, 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT), thus helping confirm that most of the serotonin observed in these experiments was neuronal in origin, and 4) lateral and medial hypothalamic microdialysis probes were used simultaneously to monitor the degree of diffusion from one to the other. The results show that extracellular serotonin increases at both sites during preingestive events as well as during eating, but not afterwards.
Penile erection can be elicited by various stimuli integrated in the spinal cord and/or higher central nervous structures. The medial preoptic area (MPOA) of the hypothalamus is known to play a key role in the regulation of male sexual behavior. In anesthetized male rats we performed MPOA stimulation via stereotaxically implanted electrodes or canulae delivering l-glutamate. An erectile response, assessed by an increase of intracarvernous pressure (ICP), was recorded during electrical stimulation of the MPOA. Stimulating the posterior region of the MPOA elicited a greater erectile response than stimulation applied to the anterior region. Microinjections of l-glutamate also elicited an ICP increase. Stimulation of MPOA neurons therefore elicits activation of neural pathways controlling penile erection.
Increased dopamine (DA) in the medial preoptic area (MPOA) facilitates male sexual behavior. A major source of innervation to the MPOA is the medial amygdala (MeA). We now report that chemical stimulation of the MeA enhanced levels of extracellular MPOA DA in anesthetized male rats. These results suggest that DA activity in the MPOA can be regulated by input from the MeA to the MPOA.
The medial preoptic area (MPOA) is an important integrative site for male sexual behavior. We have reported an increase in dopamine (DA) release in the MPOA of male rats shortly before and during copulation. Postcastration loss of copulatory ability mirrored the loss of the precopulatory DA response to an estrous female. The present study investigated the time courses of restoration, rather than loss, of the MPOA DA response to a receptive female and of copulation in long-term castrates. Male rats were castrated and tested for loss of copulatory ability 21 days later. They then received 2, 5, or 10 daily subcutaneous injections of testosterone propionate (TP, 500 μg) or oil. Microdialysate samples were collected from the MPOA during baseline, exposure to a female behind a barrier, and copulation. Extracellular DA was measured using HPLC–EC. None of the six 2-day-TP-treated animals copulated, nor did they show elevated DA release in the MPOA in the presence of a receptive female. Five of the nine 5-day-TP-treated animals ejaculated; three intromitted without ejaculating; and one failed to copulate, with all but the noncopulating animal showing elevated DA release. All of the six 10-day-TP-treated animals copulated and also demonstrated an increase in MPOA DA. None of the oil controls copulated or showed an increase in DA release. Therefore, a consistent relationship between MPOA DA release during exposure to a receptive female and the subsequent ability of the male to copulate was observed.
Male rat copulatory ability decreases dramatically following castration. This may be due in part to the impairment of medial preoptic area (MPOA) dopamine (DA) release. Previous studies showed that extracellular DA levels in the MPOA of castrates were lower than in intact males, both during basal conditions and in the presence of a receptive female. However, tissue levels of DA in the MPOA were higher in castrates than in intact males, suggesting that DA synthesis may be normal or increased in castrates, but that release may be compromised. The current study found that neither long term (2 months) nor short term (2 weeks) castration had any effect on the number of neurons in the DA A14 area that were immunoreactive (ir) for tyrosine hydroxylase (TH), the rate limiting enzyme for DA synthesis. Therefore, castration may not affect DA synthesis in the MPOA. Tissue levels of neurotransmitter reflect release, as well as synthesis. We previously reported that nitric oxide (NO) may increase DA release in the MPOA. The present study tested whether castration affected the number of NO producing cells in the MPOA. Long term, but not short term, castration significantly decreased the number of NADPH-d (nicotinamide adenine dinucleotide phosphate diaphorase) positive neurons and brain nitric oxide synthase immunoreactive (bNOS-ir) neurons in the medial preoptic nucleus (MPN). This suggests that in gonadally intact animals testosterone may activate NOS, which increases the production of NO. Long or short term castration had no effect on the numbers of bNOS-ir neurons in the paraventricular nucleus (PVN) or medial amygdala. However, short term castration decreased bNOS-ir neurons in the bed nucleus of stria terminalis (BNST). Thus, one means by which testosterone promotes male sexual behavior may be by increasing production of NO in the MPOA, which increases local DA release.
Microinjection of the dopamine antagonist cis-flupenthixol into the medial preoptic area was previously shown to impair male rat copulatory behavior. The present experiments provide further evidence of cis-flupenthixol's inhibitory effects on male sexual behavior. Following microinjections of moderate to high doses of cis-flupenthixol, males exhibited slower copulatory rates and fewer ejaculations in copula, fewer ex copula erections and penile movements, and reduced sexual motivation in an X-maze. Locomotion in the X-maze was not significantly affected. Microinjections of the inactive isomer trans-flupenthixol produced no change in any behavioral measure, indicating that cis-flupenthixol's effects were receptor mediated. We suggest that dopamine receptors in the MPOA influence copulation primarily by regulating reflexive and motivational factors, but not locomotion.
In two experiments, dopamine agonists and/or antagonists were injected into the medial preoptic area (MPOA) or the nucleus accumbens (NAcc) of male rats. The animals were then tested in an X-maze with four goal boxes, which contained a receptive female, a male, or were empty. In Experiment 1, the D1 antagonist SCH-23390 and the D2 antagonist raclopride in the MPOA decreased the percentage of trials on which the female's chamber was chosen, a measure of sexual motivation. Raclopride also decreased the number of animals that copulated after choosing the female's chamber. The 10-μg dose of the D3/D2 agonist quinelorane increased the latency to reach the female's chamber, slowed the onset of copulation, and decreased the number of intromissions preceding an ejaculation. In Experiment 2, 1- and 5-μg doses of quinelorane and of the mixed D1/D2 agonist apomorphine were injected bilaterally into the NAcc. Both doses of quinelorane increased the number of times that the subject did not select a chamber within 60 s. No drug in the NAcc affected specifically sexual motivation or performance. The results are consistent with differential influence of the MPOA and the NAcc on motor activity, sexual motivation, and sexual performance.
Serotonin (5-HT) is generally inhibitory to male rat sexual behavior. However, the 5-HT1A agonist 8-hydroxy-di-propylaminotetralin (8-OH-DPAT), injected either systemically or into the medial preoptic area (MPOA), facilitates ejaculation. Three experiments were conducted to test the effects of 8-OH-DPAT on 5-HT and dopamine (DA) neurotransmission in the MPOA, a very important site for the control of male sexual behavior. In Experiment 1, systemically injected 8-OH-DPAT (0.4 mg/kg) decreased extracellular 5-HT levels in the MPOA as measured by in vivo microdialysis. In Experiment 2, 8-OH-DPAT (500 μM) administered directly into the MPOA via reverse dialysis increased extracellular levels of both DA and 5-HT; pretreatment with the selective 5-HT1A antagonist 4-iodo-N-[2-[4-(methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinyl-benzamide hydrochloride (p-MPPI) failed to prevent 8-OH-DPAT's stimulatory effects on DA and 5-HT levels in the MPOA. In Experiment 3, 8-OH-DPAT (8 μg) co-injected with 5,7-dihydroxytryptamine (5,7-DHT; 6 μg) prevented neurotoxic depletion of 5-HT in the site of injection (MPOA). Because systemic and MPOA injections of 8-OH-DPAT resulted in opposite effects on extracellular 5-HT in the MPOA, yet both can facilitate ejaculation, these data suggest that moderate changes in 5-HT in the MPOA may have relatively little influence on male copulatory behavior. Instead, the facilitative effects of 8-OH-DPAT in the MPOA on male copulatory behavior may result, at least in part, from stimulatory effects of 8-OH-DPAT on DA transmission. Facilitative effects of systemic injections of 8-OH-DPAT may result from decreased 5-HT release in several sites.
Previous studies employing systemic administration of the dopamine agonist apomorphine have shown that the dose response curves for apomorphine's effects on penile reflexes and seminal emission differ, suggesting that experimentally separable populations of dopamine receptors regulate these two responses. The present experiments examined the locations of central nervous system DA receptors mediating genital responses in the restrained, supine rat by injecing apomorphine into the medial preoptic area and the paraventricular nucleus through chronic, indwelling cannulae. Medial preoptic area injections facilitated penile reflexes, but not seminal emission, while paraventricular injections facilitated seminal emission. These results suggest that systemically administered apomorphine may facilitate penile reflexes by acting on the medial preoptic area and may enhance seminal emission by acting on the paraventricular nucleus.
The serotonin agonist 8-hydroxy-di-propylaminotetralin (8-OH-DPAT), injected systemically or directly into the medial preoptic area (MPOA), reduces the ejaculatory threshold in male rats. While 8-OH-DPAT has been characterized as an agonist at the 5-HT1A receptor, it also acts at other receptor sites including the dopamine D2 receptor. The current experiments investigated whether 8-OH-DPAT injected into the MPOA facilitates male sexual behavior through stimulation of the 5-HT1A receptor or the dopamine D2 receptor. Experiment 1 co-administered 8-OH-DPAT (6 μg) with either the 5-HT1A antagonist 4-iodo-N-[2-[4-(methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinyl-benzamide hydrochloride (MPPI) (10 μg) or the D2 antagonist raclopride (10 μg). Raclopride blocked 8-OH-DPAT's facilitative effects on ejaculation frequency and latency, while the 5-HT1A antagonist was ineffective. In Experiment 2, 8-OH-DPAT (500 μM), retrodialyzed into the MPOA through a microdialysis probe, enhanced male copulatory behavior similarly to the microinjection, increasing ejaculation frequency and decreasing ejaculation latency, postejaculatory interval and mount frequency. Retrodialyzing 8-OH-DPAT through a microdialysis probe in the MPOA had been previously shown to increase extracellular levels of dopamine and serotonin. The data from the present studies suggest that the effects of 8-OH-DPAT in the MPOA on male rat copulatory behavior may be mediated, at least in part, either directly through 8-OH-DPAT's activity at D2 receptors or indirectly through 8-OH-DPAT's ability to increase extracellular dopamine.
Dopamine D1 and D2 receptors may synergize with or oppose each other's effects. We suggest that stimulation of D1 and D2 receptors in the medial preoptic area (MPOA) of male rats have opposing effects on genital reflexes. In Experiment 1 a D1 agonist injected into the MPOA increased the number of ex copula erections but decreased the number of seminal emissions. In Experiment 2 a D1 antagonist had the opposite effects (decreased erections and increased seminal emissions), as had a D2 agonist previously. We also suggest that D1 and D2 mechanisms in the MPOA have different thresholds of activation. In Experiment 3 a low dose of the mixed D1/D2 agonist apomorphine increased erections and anteroflexions, an effect blocked by the D1 antagonist. In Experiments 3 and 4 a high dose of apomorphine increased seminal emissions, an effect blocked by the D2 antagonist. Thus, low levels of dopaminergic stimulation may facilitate erections and anteroflexions (controlled by the parasympathetic system and striated muscles) via D1 receptors; higher or more prolonged stimulation may shift to seminal emission (controlled by the sympathetic system) via D2 receptors. This may explain the progression from erectile to ejaculatory mechanisms during copulation.
Systemically-administered dopaminergic drugs have been found to facilitate sexual behavior of men and male rats. The present experiments investigated the localization within the brain of dopaminergic effects on copulation of male rats. Apomorphine, a dopamine agonist, was microinfused into the medial preoptic area, caudate-putamen, nucleus accumbens, lateral septum and lateral ventricle. The lowest dose of apomorphine (0.2 μg) infused into the ventricle reduced the number of ejaculations, slowed the rate of intromitting and decreased the percentage of mounts on which the male gained vaginal intromission. The higher two doses (0.5 and 2.0 μg) infused into the medial preoptic area and, in some cases, the ventricle, increased the number of ejaculations and the percentage of mounts with vaginal intromission, increased the rate of intromitting and decreased the latency to ejaculate and the postejaculatory interval before resuming copulation. Infusions into the caudate-putamen and lateral septum were without effect. Those into nucleus accumbens produced only a slight dose-related decrease in latency to begin copulating. The copulatory impairments associated with infusions of the lowest dose into the ventricle may have resulted from stimulation of autoreceptors, or from preferential stimulation by low doses of an undetermined area. The facilitative effects of the two higher doses into the medial preoptic area and lateral ventricle may have been due to stimulation of dopaminergic postsynaptic receptors.
The classic dopamine agonist apomorphine, microinjected into the medial preoptic area (MPOA), enhances the copulatory behavior of male rats, while pharmacological blockade of endogenous dopamine inhibits sexual behavior. We now report that MPOA injections of 10 μg of the selective D1 agonist dihydroxyphenyl-tetrahydrothienopyridine (THP) significantly increased the number of ejaculations, while decreasing the latency to ejaculate in a 30-min test. These effects were not observed following coadministration of the selective D1 antagonist SCH-23390 with 10 μg THP. This enhancement may be related to a D1-stimulated facilitation of penile erections.