
Robert L MeiselUniversity of Minnesota | UMN · Department of Neuroscience
Robert L Meisel
PhD
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Publications (110)
Introduction
Low sexual desire is a commonly reported and often distressing form of sexual dysfunction in women. Characterized by diminished interest in sex, disinclination to initiate sex, and a loss of pleasure during sex, disorders of sexual desire among women are not only poorly understood from a psychological perspective, but also in terms of...
Introduction:
Preclinical literature, frequently utilizing rats, suggest females display a more rapid advancement of substance abuse and a greater risk of relapse following drug abstinence. In clinical populations, it is less clear as to what extent biological sex is a defining variable in the acquisition and maintenance of substance use. Even wit...
Melanocortin 3 receptors (MC3R) and melanocortin 4 receptors (MC4R) are vital in regulating a variety of functions across many species. For example, the dysregulation of these receptors results in obesity and dysfunction in sexual behaviors. Only a handful of studies have mapped the expression of MC3R and MC4R mRNA across the central nervous system...
Syrian hamsters are a valuable, if underused, model system for studying the neurobiology of aggression. Male and female hamsters live in fields where they defend territories surrounding their individual burrows. With repeated aggressive experience, hamsters show an escalation of aggression as measured by a reduction in the time to initiate an attac...
Like many social behaviors, aggression can be rewarding, leading to behavioral plasticity. One outcome of reward-induced aggression is the long-term increase in the speed in which future aggression-based encounters is initiated. This form of aggression impacts dendritic structure and excitatory synaptic neurotransmission in the nucleus accumbens, a...
Ben Sachs is one of the world’s experts on the neuroendocrine mechanisms that control sexual arousal, penile erectile function, and the expression of mating behavior in male rodents. His research laboratory produced experimental work on the respective roles of testosterone and/or its neural metabolite estradiol, acting perinatally to organize circu...
Hypoactive sexual desire disorder (HSDD) in women is a condition of low sexual desire that develops over time. Sexual desire normally diminishes over long-term relationships, but is also negatively affected by a demanding lifestyle, poor self-esteem and body image, and loss of intimacy in a relationship. HSDD elevates to a disorder when it is a con...
Our social relationships determine our health and well-being. In rodent models, there is now strong support for the rewarding properties of aggressive or assertive behaviors to be critical for the expression and development of adaptive social relationships, buffering from stress and protecting from the development of psychiatric disorders such as d...
Gonadal hormones affect neuronal morphology to ultimately regulate behavior. In female rats, estradiol mediates spine plasticity in hypothalamic and limbic brain structures, contributing to long‐lasting effects on motivated behavior. Parallel effects of androgens in male rats have not been extensively studied. Here, we investigated the effect of bo...
Gonadal hormones affect neuronal morphology to ultimately regulate behavior. Here, we investigated the effect of both castration and androgen replacement on spine plasticity in the nucleus accumbens shell and core (NAcSh and NAcC), caudate putamen (CPu), medial amygdala (MeA), and medial preoptic nucleus (MPN). Intact and castrated (GDX) male rats...
Low levels of desire and arousal are the primary sexual dysfunctions in women, necessitating neurobiological studies of sexual motivation in female animal models. As the mesocorticolimbic system is a primary neural circuit underlying sexual motivation, the goal of this study was to test the hypothesis that medial prefrontal cortex (mPFC) glutamate...
Gonadal hormones play a vital role in driving motivated behavior. They not only modulate responses to naturally rewarding stimuli, but also influence responses to drugs of abuse. A commonality between gonadal hormones and drugs of abuse is that they both impact the neurocircuitry of reward, including the regulation of structural plasticity in the n...
Although many people think of aggression as a negative or undesirable emotion, it is a normal part of many species’ repertoire of social behaviors. Purposeful and controlled aggression can be adaptive in that it warns other individuals of perceived breaches in social contracts with the goal of dispersing conflict before it escalates into violence....
The striatal brain regions, including the caudate-putamen, nucleus accumbens core, and nucleus accumbens shell, mediate critical behavioral functions. These functions include but are not limited to motivated behavior, reward, learning, and sensorimotor function in both pathological and normal contexts. The phenotype and/or incidence of all of these...
The ability to measure neurotransmitter release on a rapid time scale allows patterns of neurotransmission to be linked to specific behaviors or manipulations; a powerful tool in elucidating underlying mechanisms and circuitry. While the technique of microdialysis has been used for decades to measure nearly any analyte of interest in the brain, thi...
The hypothalamus is most often associated with innate behaviors such as is hunger, thirst and sex. While the expression of these behaviors important for survival of the individual or the species is nested within the hypothalamus, the desire (i.e., motivation) for them is centered within the mesolimbic reward circuitry. In this review, we will use f...
In comparison to men, women initiate drug use at earlier ages and progress from initial use to addiction more rapidly. This heightened intake and vulnerability to drugs of abuse is regulated in part by estradiol, although the signaling mechanisms by which this occurs are not well understood. Recent findings indicate that within the nucleus accumben...
The group I metabotropic glutamate receptors (mGluR1a and mGluR5) are important modulators of neuronal structure and function. Although these receptors share common signaling pathways, they are capable of having distinct effects on cellular plasticity. We investigated the individual effects of mGluR1a or mGluR5 activation on dendritic spine density...
Compared with men, women show enhanced responses to drugs of abuse, and consequently are thought to be more vulnerable to addiction. The ovarian hormone estradiol has emerged as a key facilitator in the heightened development of addiction in females. These actions of estradiol appear mediated by estrogen receptor (ER) activation of metabotropic glu...
The traditional approach to teaching neuroscience often involves presenting a topic like one might present a murder mystery; evidence is presented serially until he final answer is revealed. Although this approach mirrors the scientific discovery process, it is not always effective at engaging students, particularly those who are less familiar with...
Background:
Escalated aggression is a behavioral sign of numerous psychiatric disorders characterized by a loss of control. The neurobiology underlying escalated aggression is unknown and is particularly understudied in females. Research in our laboratory demonstrated that repeated aggressive experience in female hamsters resulted in an escalated...
Background:
Structural plasticity, such as changes in dendritic spine morphology and density, reflect changes in synaptic connectivity and circuitry. Procedural variables used in different methods for labeling dendritic spines have been quantitatively evaluated for their impact on the ability to resolve individual spines in confocal microscopic an...
In comparison to men, women exhibit enhanced responsiveness to the stimulating and addictive properties of cocaine. A growing body of evidence implicates the steroid hormone estradiol in mediating this sex difference, yet the mechanisms underlying estradiol enhancement of behavioral responses to cocaine in females are not known. Recently, we have f...
Accumulating evidence from human and rodent studies suggests that females are more sensitive to the motivating and rewarding properties of drugs of abuse. Numerous reports implicate estradiol in enhancing drug-related responses in females, yet the neurobiological mechanisms underlying this effect of estradiol are unknown. Because dendritic spine pl...
Female sexual behavior is an established model of a naturally motivated behavior which is regulated by activity within the mesolimbic dopamine system. Repeated activation of the mesolimbic circuit by female sexual behavior elevates dopamine release and produces persistent postsynaptic alterations to dopamine D1 receptor signaling within the nucleus...
The nucleus accumbens (NAc) is an important brain region for motivation, reinforcement, and reward. Afferents to the NAc can be divided into two anatomically-segregated neurochemical phenotypes: dopaminergic inputs, primarily from the midbrain ventral tegmental area (VTA) and glutamatergic inputs from several cortical and sub-cortical structures. A...
Motivated behaviors, including sexual experience, activate the mesolimbic dopamine system and produce long-lasting molecular and structural changes in the nucleus accumbens. The transcription factor ΔFosB is hypothesized to partly mediate this experience-dependent plasticity. Previous research in our laboratory has demonstrated that overexpressing...
Activity within the mesolimbic dopamine system is associated with the performance of naturally motivated behaviors, one of which is aggression. In male rats, aggressive behavior induces neurochemical changes within the nucleus accumbens, a key structure within the mesolimbic dopamine system. Corresponding studies have not been done in females. Fema...
This review focuses on the effects of estrogens upon the cerebellum, a brain region long ignored as a site of estrogen action. Highlighted are the diverse effects of estradiol within the cerebellum, emphasizing the importance of estradiol signaling in cerebellar development, modulation of synaptic neurotransmission in the adult, and the potential i...
Animals can switch their behavioral priorities from ingestive to sex behaviors to optimize reproductive success in environments where energy fluctuates. We hypothesized that energy availability differentially affects the appetitive (motivation), consummatory (performance), and learned (rewarding) components of behavior. In Experiment 1, appetitive...
Our knowledge about genes involved in the control of basal motor activity that may contribute to the pathology of the hyperactivity disorders, e.g., attention deficit hyperactivity disorder (ADHD), is limited. Disruption of monoamine neurotransmitter signaling through G protein-coupled receptors (GPCR) is considered to be a major contributing facto...
Identifying neuronal morphology is a key component in understanding neuronal function. Several techniques have been developed to address this issue, including Golgi staining, electroporation of fluorescent dyes, and transfection of fluorescent constructs. Ballistic delivery of transgenic constructs has been a successful means of rapidly transfectin...
Fine neuronal morphology, such as dendritic spines, classically has been studied using the Golgi technique; however, Golgi staining is difficult to combine with other histological techniques. With the increasing popularity of fluorescent imaging, a number of fluorescent dyes have been developed that enable the coupling of multiple fluorescent label...
Aggression is a major source of social stress with negative effects on health and well-being, yet limited information is known about the molecular mechanisms mediating aggressive behavior in swine. Ractopamine (RAC) is a β-adrenoreceptor agonist that enhances growth but increases aggressive behaviors in female pigs. Thus, the effects of RAC, sex, a...
Both hemispheric bias and sex differences exist in striatal-mediated behaviors and pathologies. The extent to which these dimorphisms can be attributed to an underlying neuroanatomical difference is unclear. We therefore quantified neuron soma size and density in the dorsal striatum (CPu) as well as the core (AcbC) and shell (AcbS) subregions of th...
Estradiol affects a variety of brain regions by modulating physiological and cellular functions as well as neuronal morphology. Within the striatum, estradiol is known to induce physiological and molecular changes, yet estradiol's effects on striatal dendritic morphology have not yet been evaluated. Using ballistic delivery of the lipophilic dye Di...
Under farm conditions, aggression related to the formation of social hierarchy and competition for resources can be a major problem because of associated injuries, social stress, and carcass losses. Any factor that may affect the regulation and amount of aggression within a farmed system, for instance, feeding the beta-adrenoreceptor agonist ractop...
Aggression can be a major problem for swine production as it negatively impacts the pigs' health and welfare. Increasing tryptophan (TRP) intake to raise brain serotonin (5-HT)—key for aggression control, and long-term positive social handling can reduce stress in pigs. Objective was to feed a short-term high-TRP diet to grower (3 months) and finis...
Anxiety is a classic symptom of withdrawal that often occurs in humans and animals. Preliminary studies show that anxiety in animals occurs four hours after acute morphine exposure. However, the question of the neurological structures associated with this phenomenon remains unanswered. Structures such as the central nucleus of the amygdala (CeA) an...
There is an increasing awareness that adolescent females differ from males in their response to drugs of abuse and consequently in their vulnerability to addiction. One possible component of this vulnerability to drug addiction is the neurobiological impact that reproductive physiology and behaviors have on the mesolimbic dopamine system, a key neu...
Aggression can impair productivity and well-being. The association between aggression in finishing pigs and the feed additive ractopamine (RAC), a beta-adrenoreceptor agonist, is unknown and warrants further investigation. Our goal was to examine behavioral activity, including aggression, in the home pen and concentrations of peripheral amines in b...
Repeated activation of the mesolimbic dopamine system results in persistent behavioral alterations accompanied by a pattern of neural plasticity in the nucleus accumbens (NAc). As the accumulation of the transcription factor Delta FosB may be an important component of this plasticity, the question addressed in our research is whether Delta FosB is...
Male rats received normal chow or high-fat diets rich in dextrose (HFD) or sucrose (HFS). Half of the rats received 90-day unrestricted access to their diet prior to training, whereas the other half were food restricted throughout the study. We evaluated the effects of these dietary manipulations on discrimination and reversal performance and on po...
The neurobiology of female sexual behavior has largely focused on mechanisms of hormone action on nerve cells and how these effects translate into the display of copulatory motor patterns. Of equal importance, though less studied, are some of the consequences of engaging in sexual behavior, including the rewarding properties of sexual interactions...
Glucocorticoid receptors are widely expressed in brain, where they are thought to play a role in controlling neurogenesis and to mediate many of the central nervous system effects of stress. In non-neuronal cells, protein phosphatase 5 (PP5) has been found in complexes with heat shock protein 90 and glucocorticoid receptors and may be a negative mo...
Repeated stimulation of dopaminergic pathways with dopamine receptor agonists can produce both neurochemical and behavioral sensitization.
The present study was designed to examine whether repeated treatment with the D2-like dopamine receptor agonist, quinpirole, would produce neurochemical sensitization of D1 dopamine receptor-mediated processes a...
Microdialysis measurements in the Syrian hamster clearly demonstrate a role for accumbal dopamine (DA) in female sexual behavior. However, large probe size and slow sampling rate prevent associating specific behaviors with DA changes in subregions of the heterogeneous nucleus accumbens. Fast-scan cyclic voltammetry (FSCV) at a carbon-fiber microele...
During mating in hamsters, both tactile and nontactile sensory stimulation experienced by the female affect sexual behavior and progestational neuroendocrine reflexes. To test the interactions of these types of mating stimulation, c-Fos immunohistochemistry measured brain cellular activity during sexual behavior under conditions that included combi...
Sexual experience, like repeated drug use, produces long-term changes including sensitization in the nucleus accumbens and dorsal striatum. To better understand the molecular mechanisms underlying the neuroadaptations following sexual experience, we employed a DNA microarray approach to identify genes differentially expressed between sexually exper...
This study examined the effects of sexual experience in female hamsters (Mesocricetus auratus) on copulatory interactions with male hamsters. Female sexual experience improved the copulatory efficiency of sexually naive males, an effect that persisted for at least 6 weeks without further sexual behavior testing. In a 2nd study, dopamine lesions mad...
Drugs of abuse produce long-term changes in dopamine neurotransmission and receptor-effected intracellular signaling. Similar changes in neuronal activity are mediated by motivated behaviors. To explore cellular mechanisms underlying these neuroadaptations following sexual experience, cyclic AMP accumulation following stimulation of D1 dopamine rec...
There is a substantial body of data on the interactions among hormones, reproductive behavior, and communicative behavior. However, significantly less is known about how hormones regulate social conflict and the communicative behaviors that are involved in influencing social relationships This chapter focuses on the hormonal regulation of social co...
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 pro...
The sequence of estradiol and progesterone is known to inhibit the expression of aggression in female hamsters. Despite the key importance of progesterone in the inhibition of aggression, little is known of the mechanisms through which progesterone may exert this effect. Three experiments were performed to assess the degree to which metabolites of...
Protein phosphatase 5 is a recently discovered Ser/Thr phosphatase that is structurally related to calcineurin and protein phosphatases 1 and 2. Northern blot and in situ hybridization studies have shown that protein phosphatase 5 mRNA is present at high levels in brain and is localized to discrete regions. In the present study, we used immunocytoc...
Dopamine transmission in the nucleus accumbens can be activated by drugs, stress, or motivated behaviors, and repeated exposure to these stimuli can sensitize this dopamine response. The objectives of this study were to determine whether female sexual behavior activates nucleus accumbens neurons and whether past sexual experience cross-sensitizes n...
We examined the effects of prior sexual experience on extracellular concentrations of dopamine in the nucleus accumbens of female hamsters. Nucleus accumbens dopamine was measured by in vivo microdialysis during mating in female Syrian hamsters that had previously been given six prior sexual encounters with a male, three prior encounters, or were s...
Extracellular concentrations of dopamine in the nucleus accumbens were monitored using microdialysis in ovariectomized female Syrian hamsters hormonally primed with estradiol and progesterone or with a similar regimen of oil injections. Some females in each of these groups had their vaginas occluded with tape, whereas the remaining females' vaginas...
Numerous studies have demonstrated that activation of serotonin 5-HT1A or 5-HT1B receptor decreases aggression in male mammals. To determine whether female mammals also show decreased aggression in response to 5-HT1A or 5-HT1B activation, we assessed the effects of the serotonin receptor agonists 8-OH-DPAT (5-HT1A) and CGS-12066A (5-HT1B) on aggres...
We assessed the effects of the dopamine D2 receptor antagonists, sulpiride and raclopride, on conditioned place preference produced by sexual behavior in female Syrian hamsters. Female hamsters treated with sulpiride or raclopride showed high levels of sexual behavior (lordosis) that were equivalent to control females receiving vehicle injections....
The goal of these experiments was to use c-Fos immunocytochemistry to determine areas of the female hamster brain that are active during lordosis and aggression. Ovariectomized hamsters were given (i) estradiol and progesterone, plus a lordosis test, (ii) estradiol and progesterone, but no lordosis test, (iii) oil, plus an aggressive behavior test,...
Prior studies have demonstrated the utility of conditioned place preference procedures for examining the motivational or rewarding properties of behavior. The purpose of this experiment was to assess whether female Syrian hamsters would show evidence of conditioned place preference for aggression or sexual behaviors. Weekly conditioning sessions we...
Microdialysis was used to study the effects of exposure to a male hamster on extracellular concentrations of dopamine, dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindole acetic acid (5-HIAA) in the ventral striatum of ovariectomized female Syrian hamsters pretreated with either estradiol and progesterone, or a similar...
The effects of intracranial implants of estradiol in the ventromedial hypothalamus (VMH), the anterior hypothalamus (AH), or the medial amygdala (AMG) on aggression, sexual behavior, and serum estradiol were examined in female Syrian hamsters. Estradiol implants in the VMH, followed by systemic progesterone, stimulated sexual behavior and inhibited...
The effects of intracranial implants of estradiol in the ventromedial hypothalamus (VMH), the anterior hypothalamus (AH), or the medial amygdala (AMG) on aggression, sexual behavior, and serum estradiol were examined in female Syrian hamsters. Estradiol implants in the VMH, followed by systemic progesterone, stimulated sexual behavior and inhibited...
The COOH-terminal sequence KDEL has been shown to be essential for the retention of several proteins in the lumen of the endoplasmic reticulum (Munro S., and Pelham, H. R. B. (1987) Cell 48, 899-907; Pelham, H. R. B. (1988) EMBO J. 7, 913-918; Mazzarella; R. A., Srinivasan, M., Haugejorden, S. M., and Green, M. (1990) J. Biol. Chem. 265, 1092-1101)...
We examined the effects of ovarian hormones on dendritic architecture of neurons in the ventromedial nucleus of the hypothalamus in female Syrian hamsters. Treatment with 10 μg of estradiol benzoate for two days, or estradiol benzoate for two days followed by an injection of 500 μg of progesterone, increased the total dendritic length of ventromedi...
We examined the effects of group housing on body weight in adult female Syrian hamsters. Over a 10-week period, female hamsters housed in groups of 5 per cage increased their body weight by 61% compared with an 18% increase in body weight for female hamsters housed individually. The divergence in body weight between females housed in groups and fem...
Previous studies have shown that progesterone can have biphasic activational and inhibitory roles in the regulation of sexual behavior in female Syrian hamsters. The purpose of this study was to determine whether these biphasic effects on sexual behavior are mirrored in a reciprocal regulation of aggression. Ovariectomized female Syrian hamsters we...
The effects of intracranial implants of the synthetic progestin, promegestone (R5020), on aggression and sexual behavior were examined in female Syrian hamsters. Ovariectomized female hamsters showed high levels of aggression and no lordosis towards stimulus male and female hamsters, both prior to and after estradiol benzoate treatment. Forty-six h...
These experiments were designed to test the effects of chronic estradiol treatment on aggression and sexual behavior in female hamsters. Isolated female hamsters were ovariectomized and tested for their behavioral responses to a group-housed, ovariectomized female hamster (aggression test) and a group-housed, intact male hamster (sexual behavior te...
Treatment of female rats with a low dose of estradiol (5% estradiol in a 5 mm Silastic capsule) and progesterone (0.5 mg) increased the percentage of neurons in the ventromedial nucleus of the hypothalamus that contained stacks of rough endoplasmic reticulum, as compared with female rats receiving either estradiol alone or no treatment. Only female...
The present experiments sought to identify brain regions in which implants of an antiestrogen would antagonize the ability of a systemic estradiol treatment to activate sexual behavior in female rats. In experiment 1, ovariectomized female rats were implanted subcutaneously with 5-mm Silastic capsules containing a 5% concentration of estradiol and...
A possible role of protein synthetic processes in the testosterone-activation of penile reflexes in rats was examined in these experiments. In Experiment 1, long-term castrated male rats were injected with 250 micrograms testosterone propionate (TP) and tested for penile reflexes 24 hr later. Fifteen minutes prior to TP these males received a syste...
In order to localize the neural substrate for estrogen induction of increases in activity, bilateral implants of dilute estradiol (in concentrations of 1:10, 1:100, and 1:250) were made into the medial preoptic area (n = 5), the anterior hypothalamus (n = 8), the ventromedial hypothalamus (n = 6), and the posterior hypothalamus (n = 4) of ovariecto...
These experiments were designed to investigate the role of neuronal protein synthesis in the hormonal activation of female sexual behavior using intracranial implants of the protein synthesis inhibitor, anisomycin. In the first experiment, female rats receiving bilateral cannulae implants in the medial preoptic area (POA), septal region (SEPT), ven...
The effects of long-term (15 days) and short-term (3 days) treatment with estradiol benzoate (EB) on stacking of rough endoplasmic reticulum in neurons of four brain regions (medial preoptic nucleus, ventromedial hypothalamus, arcuate nucleus and midbrain central gray) were investigated. These regions were chosen for their role in reproduction in f...