[Show abstract][Hide abstract] ABSTRACT: Intranasal application of dopamine (IN-DA) has been shown to increase motor activity and to release DA in the ventral (VS) and dorsal striatum (DS) of rats. The aim of the present study was to assess the effects of IN-DA treatment on parameters of DA and excitatory amino acid (EAA) function in prepuberal rats of the Naples high-excitability (NHE) line, an animal model for attention-deficit hyperactivity disorder (ADHD) and normal random bred (NRB) controls. NHE and NRB rats were daily administered IN-DA (0.075, 0.15, 0.30 mg/kg) or vehicle for 15 days from postnatal days 28-42 and subsequently tested in the Làt maze and in the Eight-arm radial Olton maze. Soluble and membrane-trapped L-glutamate (L-Glu) and L-aspartate (L-Asp) levels as well as NMDAR1 subunit protein levels were determined after sacrifice in IN-DA- and vehicle-treated NHE and NRB rats in prefrontal cortex (PFc), DS and VS. Moreover, DA transporter (DAT) protein and tyrosine hydroxylase (TH) levels were assessed in PFc, DS, VS and mesencephalon (MES) and in ventral tegmental area (VTA) and substantia nigra, respectively. In NHE rats, IN-DA (0.30 mg/kg) decreased horizontal activity and increased nonselective attention relative to vehicle, whereas the lower dose (0.15 mg/kg) increased selective spatial attention. In NHE rats, basal levels of soluble EAAs were reduced in PFc and DS relative to NRB controls, while membrane-trapped EAAs were elevated in VS. Moreover, basal NMDAR1 subunit protein levels were increased in PFc, DS and VS relative to NRB controls. In addition, DAT protein levels were elevated in PFc and VS relative to NRB controls. IN-DA led to a number of changes of EAA, NMDAR1 subunit protein, TH and DAT protein levels in PFc, DS, VS, MES and VTA, in both NHE and NRB rats with significant differences between lines. Our findings indicate that the NHE rat model of ADHD may be characterized by (1) prefrontal and striatal DAT hyperfunction, indicative of DA hyperactivty, and (2) prefrontal and striatal NMDA receptor hyperfunction indicative of net EAA hyperactivty. IN-DA had ameliorative effects on activity level, attention, and working memory, which are likely to be associated with DA action at inhibitory D2 autoreceptors, leading to a reduction in striatal DA hyperactivity and, possibly, DA action on striatal EAA levels, resulting in a decrease of striatal EAA hyperfunction (with persistence of prefrontal EAA hyperfunction). Previous studies on IN-DA treatment in rodents have indicated antidepressant, anxiolytic and anti-parkinsonian effects in relation to enhanced central DAergic activity. Our present results strengthen the prospects of potential therapeutic applications of intranasal DA by indicating an enhancement of selective attention and working memory in a deficit model.
[Show abstract][Hide abstract] ABSTRACT: Following oral or IV administration, dopamine (DA) cannot cross the blood-brain barrier to a significant extent, but can enter the brain when administered via the nasal passages. Intranasal administration of DA was shown to increase extracellular DA in the striatum, to have antidepressant action and to improve attention and working memory in rats. Here we show that aged (22-24 months old) rats are deficient in an object-place learning task, but that this learning/memory is intact and comparable with that of adult rats upon pre-trial administration of 0.3 mg/kg DA gel into the nasal passages. This result raises the possibility of the therapeutic application of intranasal DA treatment for age-related cognitive disorders.
Neurobiology of Learning and Memory 01/2014; · 3.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Progesterone is commonly considered as a female reproductive hormone and is well-known for its role in pregnancy. It is less well appreciated that progesterone and its metabolite allopregnanolone are also male hormones, as they are produced in both sexes by the adrenal glands. In addition, they are synthesized within the nervous system. Progesterone and allopregnanolone are associated with adaptation to stress, and increased production of progesterone within the brain may be part of the response of neural cells to injury. Progesterone receptors (PR) are widely distributed throughout the brain, but their study has been mainly limited to the hypothalamus and reproductive functions, and the extra-hypothalamic receptors have been neglected. This lack of information about brain functions of PR is unexpected, as the protective and trophic effects of progesterone are much investigated, and as the therapeutic potential of progesterone as a neuroprotective and promyelinating agent is currently being assessed in clinical trials. The little attention devoted to the brain functions of PR may relate to the widely accepted assumption that non-reproductive actions of progesterone may be mainly mediated by allopregnanolone, which does not bind to PR, but acts as a potent positive modulator of γ-aminobutyric acid type A (GABAA) receptors. The aim of this review is to critically discuss effects of progesterone on the nervous system via PR, and of allopregnanolone via its modulation of GABAA receptors, with main focus on the brain.
Progress in Neurobiology 10/2013; · 9.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Progesterone receptors (PR) are expressed throughout the brain. However, their functional significance remains understudied. Here we report a novel role of PR as crucial mediators of neuroprotection using a model of transient middle cerebral artery occlusion and PR knockout mice. Six hours after ischemia, we observed a rapid increase in progesterone and 5α-dihydroprogesterone, the endogenous PR ligands, a process that may be a part of the natural neuroprotective mechanisms. PR deficiency, and even haploinsufficiency, increases the susceptibility of the brain to stroke damage. Within a time window of 24 h, PR-dependent signaling of endogenous brain progesterone limits the extent of tissue damage and the impairment of motor functions. Longer-term improvement requires additional treatment with exogenous progesterone and is also PR dependent. The potent and selective PR agonist Nestorone is also effective. In contrast to progesterone, levels of the neurosteroid allopregnanolone, which modulates γ-aminobutyric acid type A receptors, did not increase after stroke, but its administration protected both wild-type and PR-deficient mice against ischemic damage. These results show that 1) PR are linked to signaling pathways that influence susceptibility to stroke, and 2) PR are direct key targets for both endogenous neuroprotection and for therapeutic strategies after stroke, and they suggest a novel indication for synthetic progestins already validated for contraception. Although allopregnanolone may not be an endogenous neuroprotective agent, its administration protects the brain against ischemic damage by signaling mechanisms not involving PR. Collectively, our data clarify the relative roles of PR and allopregnanolone in neuroprotection after stroke.
[Show abstract][Hide abstract] ABSTRACT: Progesterone is well known as a female reproductive hormone and in particular for its role in uterine receptivity, implantation, and the maintenance of pregnancy. However, neuroendocrine research over the past decades has established that progesterone has multiple functions beyond reproduction. Within the nervous system, its neuromodulatory and neuroprotective effects are much studied. Although progesterone has been shown to also promote myelin repair, its influence and that of other steroids on myelination and remyelination is relatively neglected. Reasons for this are that hormonal influences are still not considered as a central problem by most myelin biologists, and that neuroendocrinologists are not sufficiently concerned with the importance of myelin in neuron functions and viability. The effects of progesterone in the nervous system involve a variety of signaling mechanisms. The identification of the classical intracellular progesterone receptors as therapeutic targets for myelin repair suggests new health benefits for synthetic progestins, specifically designed for contraceptive use and hormone replacement therapies. There are also major advantages to use natural progesterone in neuroprotective and myelin repair strategies, because progesterone is converted to biologically active metabolites in nervous tissues and interacts with multiple target proteins. The delivery of progesterone however represents a challenge because of its first-pass metabolism in digestive tract and liver. Recently, the intranasal route of progesterone administration has received attention for easy and efficient targeting of the brain. Progesterone in the brain is derived from the steroidogenic endocrine glands or from local synthesis by neural cells. Stimulating the formation of endogenous progesterone is currently explored as an alternative strategy for neuroprotection, axonal regeneration, and myelin repair.
[Show abstract][Hide abstract] ABSTRACT: l-3,4-Dihydroxyphenylalanine (L-DOPA) remains the most effective drug for therapy of Parkinson's disease. However, the current clinical route of L-DOPA administration is variable and unreliable because of problems with drug absorption and first-pass metabolism. Administration of drugs via the nasal passage has been proven an effective alternate route for a number of medicinal substances. Here we examined the acute behavioral and neurochemical effects of intranasally (IN) applied L-DOPA in rats bearing unilateral lesions of the medial forebrain bundle, with severe depletion (97%) of striatal dopamine. Turning behavior in an open field, footslips on a horizontal grid and postural motor asymmetry in a cylinder were assessed following IN L-DOPA or vehicle administration with, or without, benserazide pre-treatment. IN L-DOPA without benserazide pre-treatment mildly decreased ipsilateral turnings and increased contralateral turnings 10-20 min after the treatment. IN L-DOPA with saline pre-treatment reduced contralateral forelimb-slips on the grid while no effects were evident in the cylinder test. These results support the hypothesis that L-DOPA can bypass the blood-brain barrier by the IN route and alleviate behavioral impairments in the hemiparkinsonian animal model.
Brain research bulletin 11/2011; 87(2-3):340-5. · 2.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Neurosteroids hold great promise for the treatment of diseases of the central nervous system (CNS). We compared the uptake by 11 brain regions and appearance in blood of tritium-labeled pregnenolone and progesterone after intranasal and intravenous (IV) injection. Both neurosteroids appeared in blood and brain after either method of administration, but with important differences in uptake. Bioavailability based on appearance in arterial serum showed that about 23% and 14% of the intranasal administered doses of pregnenolone and progesterone, respectively, entered the blood. Brain levels were about two fold lower after intranasal administration for the two neurosteroids. With intranasal administration, brain levels of the two steroids did not vary over time (2-120 min), whereas brain levels were higher early (10 min or less) after i.v. administration. With i.v. administration, uptake by brain regions did not vary, whereas the olfactory bulb, hippocampus, and hypothalamus had high uptake rates after intranasal administration. Intranasal administration of prenenolone improved memory, whereas progesterone decreased anxiety, thus demonstrating that therapeutic levels of neurosteroids can be delivered to the brain by intranasal administration. The neurosteroids were rapidly degraded after i.v. or intranasal delivery, but pregnenolone was more resistant to degradation in the brain after intranasal administration and in serum after i.v. administration. These results show that either the i.v. or intranasal routes of administration can deliver neurosteroids to blood and brain, but that the two routes have significant differences with intranasal administration favoring some brain regions.
European journal of pharmacology 09/2010; 641(2-3):128-34. · 2.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Testosterone influences various aspects of affective behavior, which is mediated by different brain regions within the emotion circuitry. Previous neuroimaging studies have demonstrated that testosterone increases neural activity in the amygdala. To investigate whether this could be due to altered regulation of amygdala functioning which is thought to be mediated by the prefrontal cortex, we studied the effects of exogenous testosterone on the interaction between the amygdala and other brain regions. Healthy middle-aged women received a single nasal testosterone dose in a randomized, placebo-controlled, crossover manner, and performed an emotional face matching task while their brain activity was measured with functional MRI. The results show that testosterone rapidly reduced functional coupling of the amygdala with the orbitofrontal cortex, and enhanced amygdala coupling with the thalamus. This suggests that testosterone may reduce the regulatory control over the amygdala, or that testosterone shifts amygdala output away from the orbitofrontal cortex towards the thalamus. Testosterone also reduced functional coupling with the contralateral amygdala. Because interhemispheric amygdala coupling is lower in men than in women, this result suggests that circulating testosterone may contribute to this sexual dimorphism.
[Show abstract][Hide abstract] ABSTRACT: Due to its lipophobic properties, dopamine is unable to cross the blood-brain barrier following systemic application. However, recently it has been demonstrated that, when applied directly via the nasal passages in the rat, dopamine exerts neurochemical and behavioural action, including increases of dopamine in striatal subregions, antidepressive-like action, and increased behavioral activity. These effects could potentially be mediated by exogenous dopamine acting as a direct agonist at postsynaptic dopamine receptors. However, it is also possible that intranasally applied dopamine acts indirectly via the modulation of the activity of dopaminergic cell bodies. To approach this question, the present study used rats with unilateral 6-hydroxydopamine (6-OHDA) lesions of the nigrostriatal tract, as these lesions lead to pharmacologically stimulated behavioural asymmetries which are specific for direct and indirect dopamine agonists. We found that 7 days of repeated treatment with intranasal dopamine induced a sensitization of the turning response to amphetamine, but not to apomorphine. Furthermore, intranasal dopamine dose-dependently increased the use of the forepaw ipsilateral to the 6-OHDA-lesioned side of the brain. These results suggest that intranasally administered dopamine acts via an indirect mechanism of action, putatively by increasing the release of endogenous dopamine in the brain.
[Show abstract][Hide abstract] ABSTRACT: Based on findings of a profound action of intranasally applied dopamine (DA) on dopamine release in the striatum, we examined the possibility that intranasal application of DA would influence indices of attention and activity in juvenile male rats of the Naples High Excitability line. This rat model features the main aspects of Attention Deficit/Hyperactivity Disorder (ADHD). Juvenile NHE rats received an intranasal application of either DA (0.075 mg/kg, 0.15 mg/kg and 0.3 mg/kg) or vehicle into both nostrils daily for 15 days. On day 14, 1 h after treatment, they were tested in the Làt maze, and one day later, in the eight arm radial maze. Activity in the Làt maze: The highest dose of DA (0.3 mg/kg) decreased horizontal (HA) and vertical (VA) activity during the first 10 min of the test. No effect was found for rearing duration (RD), which indexes non-selective attention (NSA). Activity in the radial maze: No treatment effects were found for HA and VA components, and for RD. Attention indices: The intermediate dose of DA (0.15 mg/kg) significantly improved the number of arms visited before the first repetitive arm entry in the radial maze, an index of selective spatial attention (SSA). In conclusion, intranasal application of DA reduced hyperactivity at the highest dose used, whereas the intermediate dose improved attention in an animal model of ADHD. These results suggest the potential of employing intranasal DA for therapeutic purposes.
European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 04/2009; 19(10):693-701. · 3.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Although multiple forms of testosterone replacement therapy are available to treat hypogonadism, none is ideal. This article reports on the pharmacokinetics of an innovative nasal formulation of testosterone in hypogonadal men. The first study was undertaken in eight men with a baseline total testosterone (TT) of 130.8 +/- 87.4 ng/dL and examined the pharmacokinetics of nasal testosterone given in a single dose of 7.6 mg, 15.2 mg or 22.8 mg, respectively. The second study examined the pharmacokinetics of nasal testosterone (7.6 mg) given either twice or three times a day in 21 severely hypogonadal men (baseline TT in 20 patients <50 ng/dL, in one patient 152 ng/dL) for 14 days. The steady-state concentration of testosterone was within the normal range in all treatment groups, but only in the 3-times-a-day group was the 95% confidence interval completely within the physiological range. The average DHT level did not exceed the upper range of normal. The clinical global visual analogue scale improved in the whole group receiving testosterone (p < 0.001). All adverse events in both studies were of mild to moderate intensity and were evaluated as unlikely or not related to the administered study drug. No patients dropped out during treatment. Comparison with the normal circadian rhythm by computer modelling suggests that nasal testosterone can be used to mimic the normal diurnal pattern in eugonadal men. Thus, nasal testosterone can be administered safely to humans in doses that approximate serum concentrations in the normal physiological range.
The Aging Male 01/2009; 11(4):171-8. · 1.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Intranasal (i.n.) administration has emerged as a strategy to deliver therapeutics to the brain. Here, we compared i.n. and intravenous (i.v.) administration for testosterone. About 75% of the i.n. administered testosterone entered the blood. However, whole brain levels of testosterone were about twice as high after i.n. administration as after i.v. administration. About two-thirds of the testosterone entering the brain after i.n. administration did so by direct entry by nasal routes and the remainder indirectly by first entering the blood and then crossing the blood-brain barrier. All brain regions except the frontal cortex had higher levels of testosterone after i.n. administration than after i.v. administration, although the differences among brain regions varied much more for the i.n. route. The olfactory bulb, hypothalamus, striatum, and hippocampus had the highest levels after i.n. administration. The brain uptake pattern suggested a variety of distribution routes likely involving the cerebrospinal fluid, diffusion through brain tissue, and transport through nerve projections. Regional distribution patterns were similar after either i.n. or i.v. administration, suggesting that the dominant factor determining distribution/retention was the same for either route of administration. We conclude that the i.n. administration route delivers testosterone systemically and can target the brain, especially the olfactory bulb, hypothalamus, striatum, and hippocampus.
Journal of Drug Targeting 01/2009; 17(2):91-7. · 2.77 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Testosterone was administered intranasally in anesthetized male rats, and its effects on the activity of dopaminergic and serotonergic neurons in the neostriatum and nucleus accumbens were assessed by means of microdialysis and HPLC. The treatment (0.5, 1.0 or 2.0 mg/kg of testosterone or vehicle, 10 microl volume) was applied in both nostrils, half (5 microl) into each. Subcutaneous injections of testosterone (2.0, 4.0 or 8.0 mg/kg) or vehicle were tested in other subjects. Samples were collected for 5 h. In the neostriatum, an increase of dopamine occurred after 2.0 mg/kg. Serotonin levels increased after 1.0 mg/kg dose. In the nucleus accumbens, dopamine and serotonin increased after 1.0 mg/kg and 2.0 mg/kg doses. Subcutaneous administration of 8.0 mg/kg testosterone increased dopamine and serotonin in the neostriatum only. We conclude that intranasal administration of testosterone is a more efficacious way for targeting the brain than the subcutaneous route, and may be considered as a means to activate central dopaminergic and serotonergic systems.
European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 10/2008; 19(1):53-63. · 3.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We evaluated the effects of intranasal administration of progesterone (PROG) on the activity of dopaminergic neurons in the brain of anesthetized rats by means of microdialysis. Male Wistar rats were implanted with guide cannulae in the basolateral amygdala and neostriatum. Three to 5 days later, they were anesthetized with urethane, and dialysis probes were inserted. After a stabilization period of 2 h, four 30-min samples were collected. Thereafter, the treatment (0.5, 1.0 or 2.0 mg/kg of PROG dissolved in a viscous castor oil mixture, or vehicle) was applied into the nose in a volume of 10 microl (5 microl in each nostril). In other animals, an s.c. injection of PROG (1.0, 2.0 or 4.0 mg/kg) or vehicle was given. Samples of both application ways were collected at 30-min interval for 4 h after the treatment and immediately analyzed with high performance liquid chromatography and electrochemical detection. Intranasal administration of 2 mg/kg of PROG led to an immediate (within 30 min after the treatment) significant increase in the basolateral amygdala dopamine levels. In the neostriatum, the 2 mg/kg dose led to a delayed significant increase in dopamine. S.c. administration of 4 mg/kg of PROG was followed by a delayed significant increase in dopamine, both, in the basolateral amygdala and neostriatum, but smaller in magnitude in comparison to the intranasal treatment. This is the first study to demonstrate dopamine-enhancing effects of PROG, not only in the neostriatum, but also in the basolateral amygdala. Our results indicate that the intranasal route of administration of PROG is a more efficacious way for targeting the brain than the s.c. route.
[Show abstract][Hide abstract] ABSTRACT: Female mate choice involves the comparative evaluation of potential mates. Females use a pooled comparison of sampled males to maximize the perceived reproductive fitness of their partner, implying the memorization of sampled males. However, hormonal and reproductive states influence female choosiness, and women's preference and memory for masculinity. Here, we investigated whether testosterone biases memory processes in women towards male faces using functional MRI. A single nasal testosterone dose was administered to healthy women in their early follicular phase, in a double-blind, placebo-controlled, crossover design. Testosterone increased the difference in reaction times to categorize male and female faces during encoding, without influencing subsequent recognition accuracy or response bias. The imaging results showed that testosterone shifted memory formation in the hippocampus and inferior temporal gyri from the encoding of female faces towards the encoding of male faces. In contrast, testosterone shifted memory formation in the left inferior frontal gyrus from the encoding of male faces towards the encoding of female faces. Furthermore, the hippocampal contribution to memory retrieval also shifted from female towards male faces. These results indicate that testosterone biases memory processes towards the relatively automatic encoding and retrieval of males in temporal brain regions and elaborate encoding of females in frontal brain regions, suggesting that testosterone may support female mate sampling and comparison by biasing automatic memory processes towards the encoding and retrieval of potential mates.
[Show abstract][Hide abstract] ABSTRACT: Dopamine (DA) plays an important role in a number of behavioral processes and neurological disorders. The intranasal administration of DA provides improved brain penetrability in comparison to systemic administration. We investigated the effects of intranasal administration of DA on the activity of dopaminergic neurons of the mesostriatal and mesolimbic systems and on motor activity. Rats previously implanted with guide-cannulae in the neostriatum (NS) and nucleus accumbens (NAc) were submitted to microdialysis procedure under urethane anesthesia. Vehicle or DA (0.03, 0.3, or 3.0 mg/kg) was administered bilaterally into the nostrils. In a separate study, animals received an intraperitoneal (i.p.) injection of vehicle or DA (0.03, 0.3, 3.0, or 30.0 mg/kg). Samples were collected every 10 min and analyzed for the content of DA and metabolites using high-performance liquid chromatography. For the open field study, rats were given intranasal vehicle or DA (0.03, 0.3, or 3.0 mg/kg) and placed into the field for 30 min. Motor activity (locomotion and rearing) and grooming were analyzed in blocks of 10 min using Ethovision. Intranasal DA (3.0 mg/kg) significantly increased DA levels in the NS and NAc immediately after administration. A comparable effect was obtained only after i.p. administration of 30 mg/kg DA. In the open field, the 3.0 mg/kg dose significantly decreased grooming behavior in the second 10 min interval and significantly increased locomotor activity in the third 10 min interval. The data indicate that intranasal administration of DA can influence dopaminergic functions and motor activity, and has a potential application in the therapy of diseases affecting the dopaminergic system.
[Show abstract][Hide abstract] ABSTRACT: Testosterone modulates mood and sexual function in women. However, androgen levels decline with age, which may relate to the age-associated change in sexual functioning and the prevalence of mood and anxiety disorders. These effects of testosterone are potentially mediated by the amygdala. In the present study, we investigated whether the age-related decline in androgen levels is associated with reduced amygdala activity, and whether exogenous testosterone can restore amygdala activity. Healthy young and middle-aged women participated during the early follicular phase of the menstrual cycle, and amygdala responses to biologically salient stimuli were measured with functional magnetic resonance imaging (fMRI). Androgen levels were lower in middle-aged than young women, which was associated with decreased amygdala reactivity. Endogenous testosterone levels correlated positively with amygdala reactivity across the young and middle-aged women. The middle-aged women received a single nasal dose of testosterone in a double-blind, placebo-controlled, crossover manner, which rapidly increased amygdala reactivity to a level comparable to the young women. The enhanced testosterone levels correlated positively with superior frontal cortex responses and negatively with orbitofrontal cortex responses across individuals, which may reflect testosterone-induced changes in amygdala regulation. These results show that testosterone modulates amygdala reactivity in women, and suggest that the age-related decline in androgen levels contribute to the decrease in amygdala reactivity.
Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 02/2008; 34(3):539-47. · 8.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Recently, we found evidence that intra-nasally administered dopamine (DA), can enter the brain, leading to an immediate increase in extracellular DA levels in striatal subregions. This offers a potential alternative approach to target the brain with exogenous DA, which otherwise cannot cross the blood-brain barrier. Here, we examined whether intra-nasally applied DA also exerts behavioral activity on mesocortical and nigrostriatal dopaminergic functions.
Male Wistar rats (3-4 months) were tested for potential behavioral effects of intra-nasally applied DA (0.03, 0.3 or 3.0 mg/kg) in the forced swimming test (FST) for antidepressant-like activity, elevated plus-maze for anxiety-related behavior, and on motor activity in a novel and familiar environment.
Intra-nasally administered dopamine in a dose of 0.3 mg/kg exerted antidepressant-like activity in the FST, but had neither anxiolytic-like nor anxiogenic-like effects in the elevated plus-maze. Furthermore, intra-nasal dopamine stimulated locomotor activity in a familiar, but not novel, open field.
These results support the view that intra-nasally applied DA can act on the central nervous system by entering the brain via the nose-brain pathway, making this kind of application procedure a promising alternative for targeting the brain, and thus treating disorders involving mesocortical and/or nigrostriatal dopaminergic disturbances.
[Show abstract][Hide abstract] ABSTRACT: Sexual dysfunction in the female has been associated with a decrease in androgen levels, which can be reversed by testosterone treatment, however, bearing the risk of adverse side effects. Nasally administered testosterone could be an effective method for androgenic treatment avoiding the first-pass intestinal and hepatic metabolism and side effects. Here we examined the effects of chronic intranasal administration of testosterone on sexual behavior in female capuchin monkeys (Cebus apella) that lived with male cohorts. During 8 days of baseline 10 females were observed for their sexual and non-sexual behavior without drug. They then received daily intranasal testosterone (0.24 mg per nostril, n=5 per group) or placebo gel for 5 days, followed by 5 days of wash out, followed by 5 days of daily intranasal application, whereby the animals that had received testosterone before, now received placebo and vice versa. Diverse sexual and non-sexual behaviors were scored. Blood samples were collected and analyzed for testosterone, estradiol, dihydrotestosterone and progesterone using EIAs. The results revealed an increase in sexual behavior (eyebrow raising, chest rubbing, courtship behavior, masturbation) in the females during testosterone treatment, which seemed to be prolonged even when testosterone treatment was discontinued. These behavioral results were accompanied by an increase in plasma testosterone levels. This study demonstrates the efficacy of testosterone in enhancing sexual behavior in female capuchin monkeys by means of intranasal application, which may be a useful alternative compared to other forms of administration.
Behavioural Brain Research 05/2007; 179(1):33-42. · 3.33 Impact Factor