Is sexual motivational state linked to dopamine release in the medial preoptic area?

The medial preoptic area (mPOA) is a key site for the dopaminergic enhancement of male sexual behavior. Dopamine release increases in the rat mPOA with mating, supporting the critical stimulatory role played by preoptic dopamine on male sexual behavior. However, it has been questioned whether dopamine is specifically related to the occurrence of male sexual behavior and not simply involved in general arousal. To address this question, we asked whether dopamine release in the mPOA is linked to the production of male sexual behavior in Japanese quail (Coturnix japonica), a species that exhibits a much shorter temporal pattern of copulation than rats and does not have an intromittent organ, resulting in a very different topography of their sexual response. Extracellular samples from the mPOA of adult sexually experienced male quail were collected every 6 min before, during, and after exposure to a female using in vivo microdialysis and analyzed using high-performance liquid chromatography with electrochemical detection. Extracellular dopamine significantly increased in the presence of a female and returned to baseline after removal of the female. However, quail that failed to copulate did not display this increased release. These findings indicate that it is not solely the presence of a female that drives dopamine release in males, but how a male responds to her. Furthermore, in quail that copulated, dopamine release did not change in samples collected during periods of no copulation. Together, these findings support the hypothesis that dopamine action in the mPOA is specifically linked to sexual motivation and not only to copulatory behavior or physical arousal. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Mating activates NMDA receptors in the medial preoptic area of male rats.

Studies have emphasized the role of the medial preoptic area (MPOA) as an important site for the regulation of male sexual behavior. Indeed, ablations of the MPOA impair sexual behavior, whereas stimulation of the MPOA enhances behavior. Furthermore, neural activity in the MPOA increases with mating. The current study tested the hypothesis that activation of N-methyl-D-aspartate (NMDA) receptors occurs in MPOA neurons and is essential for the expression of male sexual behavior in rats. Results indicate that nearly all MPOA neurons that expressed Fos following mating also contained the NR1 subunit of NMDA receptors. Furthermore, mating increased phosphorylation, thus activation, of NR1 in the MPOA. Additionally, blocking NMDA receptors significantly decreased mating-induced Fos expression and mating-induced phosphorylation of NMDA receptors and impaired male sexual behavior. These results provide evidence that mating activates NMDA receptors in the MPOA and that this activation is important for the expression of male sexual behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Electrical stimulation of dorsal and ventral striatum differentially alters the copulatory behavior of male rats.

Sexual behavior is a natural reward that activates striatal dopaminergic (DA) circuits, and dopamine exerts a facilitative influence on copulation. Electrical stimulation of the striatum has been shown to be rewarding, but its effect on male sexual behavior display has not been established. The objective of the present work was to assess the effects of low- and high-frequency electrical stimulation of the dorsal and ventral striatum on male rat sexual behavior expression. To this aim, copulatory activity of sexually experienced male rats was recorded during electrical stimulation of the nucleus accumbens (NAcc) or caudate-putamen (CP), at each stimulation frequency, before and after sexual exhaustion. Results showed that electrical stimulation of the NAcc at both frequencies increased the number of ejaculations that male rats were able to show in a 30-min period. By contrast, stimulation delivered to the CP inhibited sexual behavior by slowing its display. Each effect was more pronounced at low than at high stimulation frequencies. In the same rats, once sexually exhausted, electrical stimulation of these brain areas did not reverse the sexual behavior inhibition that characterizes the sexual exhaustion state. It is concluded that dorsal and ventral striatal DA brain regions exert opposite influences on copulatory behavior expression of sexually experienced male rats. Also, that the facilitative effect of NAcc electrical stimulation on sexual activity, with the stimulation parameters used, cannot surmount the sexual behavior inhibition resulting from copulation to satiation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sexual experience increases nitric oxide synthase in the medial preoptic area of male rats.

Nitric oxide in the medial preoptic area (MPOA) is important for the expression and sensitization of male sexual behavior. In this article, the authors report that repeated sexual experience (mating for 2 hr on each of 3 days) increased levels of nitric oxide synthase (NOS) in the MPOA of male rats, regardless of whether they mated on the day they were given an overdose of sodium phenobarbital. This effect resulted from the previous experience and not acute mating, as NOS was not increased 2 hr after the first mating in previously naive males. Experience-induced increases in NOS in the MPOA may be one mechanism through which sexual experience facilitates sexual behavior in male rats. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

6-Hydroxydopamine Lesions in Female Hamsters (Mesocricetus auratus) Abolish the Sensitized Effects of Sexual Experience on Copulatory Interactions With Males.

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 made in the region of the nucleus accumbens prior to sexual experience specifically blocked the effects of the female's sexual experience on the hit rate of naive males. These results suggest that sexual experience in female hamsters increases the efficiency of copulatory interactions with males, that these effects persist in the absence of further sexual experience, and that dopamine neurotransmission in the basal forebrain underlies this effect of sexual experience. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The paternally expressed gene Peg3 regulates sexual experience-dependent preferences for estrous odors.

Sexual experience has marked and long-lasting effects on male behavior in mammals, regulating traits such as the anticipation and display of sexual behavior, aggression, and olfaction. The authors conducted urine preference, habituation-dishabituation, and partner choice tests with sexually experienced and naive male mice and found that wild-type males acquire adaptively significant preferences for the odors of receptive, estrous females with sexual experience, and that these preferences are matched by changes in main olfactory system responses involving the piriform cortex, as indicated by c-Fos expression. The authors also report that these experiential effects are disrupted in male mice carrying a knockout of the imprinted gene Peg3. This paternally expressed gene regulates maternal care and offspring development, but the authors here report that Peg3 mutant males suffer a complex olfactory deficit that affects estrous odor preferences and the responses of the main olfactory system to such odors. Peg3 appears to have evolved to regulate the experience-dependent preference for receptive females, an adaptive trait that would enhance male reproductive success and so potentially increase paternal transmission of this paternally expressed gene. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Unconditioned sexual incentive motivation in the male Norway Rat (Rattus norvegicus).

Sexual incentive motivation was evaluated in a procedure consisting of a large open field where incentive animals were confined behind wire mesh openings. When sexually inexperienced male rats (Rattus norvegicus) were exposed to the receptive female-male incentives, they spent more time close to the female. If the incentives were receptive female-nonreceptive female, the receptive female was preferred. However, when the alternatives were nonreceptive female-male, no preference was obtained. Castration abolished preference for the receptive female, and treatment with testosterone propionate restored it. Estradiol plus oil is as efficient as estradiol plus progesterone for giving the ovariectomized female incentive properties. The living female can be replaced with female odor. Sexual experience did not have any long-term effects on the female's incentive value, but immediately preceding limited sexual activity enhanced it. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of ibotenic acid lesions of the nucleus accumbens on paced mating behavior in the female rat.

The present study investigated the role of the nucleus accumbens (NAcc) in paced mating behavior in female rats. A sexually receptive female rat will approach and withdraw from a sexually active male, thereby controlling the timing of the receipt of sexual stimulation (e.g., mounts, intromissions, ejaculations). In this study, ibotenic acid lesions in the NAcc core increased the likelihood that a female rat would withdraw from a male rat after a mount but did not affect contact return latency or sexual receptivity. lbotenic acid lesions in the NAcc shell did not affect paced mating behavior or sexual receptivity. The results suggest that the NAcc core plays a role in suppressing withdrawal behavior in response to less intense mating stimulation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Lead toxicosis in a captive bottlenose dolphin (Tursiops truncatus) consequent to ingestion of air gun pellets

Male rats of the Wistar strain were selected as good copulators (displaying at least 1 ejaculation in each of three consecutive tests for male sexual behavior) and sexually sluggish animals (displaying no ejaculations in each of three consecutive tests). The administration of low doses (1 and 2.5 mg/kg, i.p.) of kainic acid in sexually sluggish rats induced an enhancement of some parameters of copulatory behavior. In particular, significant reductions in latency to the first mount and intromission and increases in frequency of mounts and intromissions were observed. In contrast, the drug failed to exert any effect in good copulators. At the dose of 5 mg/kg (i.p.) kainic acid exerted an inhibitory effect on sexual behavior parameters both in good copulators and in sluggish rats. A persistent increase in latency to the first mount, intromission and ejaculation, and reduction in frequency of mounts, intromissions and ejaculation both in good copulators and in sluggish rats were observed 20 days after kainic acid treatment at the higher dose. No persistent effect of kainic acid 1 and 2.5 mg/kg was observed 20 days after treatment. These results suggest that kainic acid may affect in a dose-dependent manner several copulatory parameters of male sexual behavior repertoire. The bimodal effects could be explained considering a possible interaction of kainic acid with different neurotransmissions or receptor subtypes.     

Lack of opioid or dopaminergic effects on unconditioned sexual incentive motivation in male rats.

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. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

NMDA receptor activation during status epilepticus is required for the development of epilepsy

NMDA receptor activation has been implicated in modulating seizure activity; however, its complete role in the development of epilepsy is unknown. The pilocarpine model of limbic epilepsy involves inducing status epilepticus (SE) with the subsequent development of spontaneous recurrent seizures (SRSs) and is widely accepted as a model of limbic epilepsy in humans. The pilocarpine model of epilepsy provides a tool for looking at the molecular signals triggered by SE that are responsible for the development of epilepsy. In this study, we wanted to examine the role of NMDA receptor activation on the development of epilepsy using the pilocarpine model. Pretreatment with the NMDA receptor antagonist MK-801 does not block the onset of SE in the pilocarpine model. Thus, we could compare animals that experience similar lengths of SE in the presence or absence of NMDA receptor activation. Animals treated with MK-801 (4 mg/kg) 20 min prior to pilocarpine (350 mg/kg) (MK-Pilo) were compared to the pilocarpine treated epileptic animals 3-8 weeks after the initial episode of SE. The pilocarpine-treated animals displayed both ictal activity and interictal spikes on EEG analysis, whereas MK-801-pilocarpine and control animals only exhibited normal background EEG patterns. In addition, MK-801-pilocarpine animals did not exhibit any SRSs, while pilocarpine-treated animals exhibited 4.8 +/- 1 seizures per 40 h. MK-801-pilocarpine animals did not demonstrate any decrease in pyramidal cell number in the CA1 subfield of the hippocampus, while pilocarpine animals averaged 15% decrease in cell number. In summary, the MK-801-pilocarpine animals exhibited a number of characteristics similar to control animals and were statistically significantly different from pilocarpine-treated animals. Thus, NMDA receptor inhibition by MK-801 prevented the development of epilepsy and interictal activity following SE. These results indicate that NMDA receptor activation is required for epileptogenesis following SE in this model of limbic epilepsy.     

Spatial memory and N-methyl-D-aspartate receptor antagonists APV and MK-801: Memory impairments depend on familiarity with the environment, drug dose, and training duration.

Rats given N-methyl-D-aspartate (NMDA) antagonists were tested in the radial maze in spatial working memory (WM) and reference memory (RM) tasks. 16 female rats given (+)-10,11-dihydro-5-methyl-5H-dibenzo [a,d] cycloheptene-5,10 imine (MK-801; 0.0625 mg/kg intraperitoneal/ly (ip)) before daily testing in an 8-arm WM task were impaired even after 70 days. Control rats learned quickly, were assigned to a group given MK-801 or saline, and were trained to avoid 4 of the 8 arms. MK-801 impaired this reversal learning but did not affect WM performance. 15 male rats were trained on an 8-arm WM task for 19 days and then given intracranial aminophosphonovaleric acid (APV; 33 mM), which impaired both WM and motor behavior. 24 male rats were trained for 65 days to enter 4 of 8 arms and then given intracranial APV (20 or 30 mM). WM and RM were normal in the familiar environment but were both impaired in an unfamiliar environment. Results suggest that the mnemonic effects of NMDA antagonists depend on environmental familiarity, dose, and training duration. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Characterization of ionotropic glutamate receptor-mediated nitric oxide production in vivo in rats

BACKGROUND AND PURPOSE: Glutamate receptor activation can stimulate nitric oxide (NO) production and possibly play a role in long-term potentiation and excitotoxic-mediated injury. We studied the differential effect of agonist-induced activation of ion channel-linked N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor subtypes on NO production in vivo in rat hippocampus. We also studied whether dantrolene, a ryanodine calcium channel inhibitor previously shown to attenuate metabotropic glutamate receptor stimulation of NO production, also attenuated ionotropic glutamate receptor-mediated stimulation of NO production. METHODS: Microdialysis probes were placed bilaterally into the CA3 region of the hippocampus of pentobarbital-anesthetized adult Sprague-Dawley rats and were perfused for 5 hours with artificial cerebrospinal fluid (CSF) containing 3 mumol/L [14C]L-arginine. Recovery of [14C]L-citrulline in the effluent was used as a marker of NO production. In 13 groups of rats, increases in [14C]L-citrulline recovery were compared between right- and left-sided probes perfused with no additional drugs versus combinations of NMDA, AMPA, the NO synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME), the non-competitive glutamate receptor blocker MK-801, the AMPA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), and dantrolene. RESULTS: Recovery of [14C]L-citrulline during perfusion with artificial CSF progressively increased to 272 +/- 73 fmol/min (+/-SEM) over 5 hours. Contralateral perfusion with 1 mmol/L L-NAME inhibited [14C]L-citrulline recovery. Perfusion with 1 mmol/L MK-801 or 1 mmol/L CNQX reduced [14C]L-citrulline recovery compared with contralateral perfusion with CSF alone. Perfusion with 1 mmol/L NMDA enhanced [14C]L-citrulline recovery, and this enhancement was attenuated by L-NAME, MK-801, and CNQX but not by dantrolene. Perfusion with 1 mmol/L AMPA enhanced [14C]L-citrulline recovery, and this enhancement was also attenuated by L-NAME, MK-801, and CNQX but not by dantrolene. CONCLUSIONS: Through an indirect method of assessing NO production in vivo, results with MK-801 and CNQX indicate that NMDA and AMPA receptor activation contribute to basal NO production in the rat hippocampus. Enhanced NO production with NMDA and AMPA agonists appears to involve a complex neuronal interaction because the effect of NMDA was attenuated by both MK-801 and CNQX and because the effect of AMPA was attenuated by both CNQX and MK-801. In contrast to metabotropic glutamate receptor activation, release of calcium from intracellular ryanodine calcium channels does not appear to be a prominent mediator of ionotropic glutamate receptor stimulation of NO production.     

Coexpression of sexual behavior and maternal aggression: The ambivalence of sexually active mother rats toward male intruders.

The sexually active female rat solicits the male to approach for copulation, while the maternal dam displays aggression to expel him from the nest, suggesting that both behaviors are mutually exclusive. However, the rat has a postpartum estrus during which she is sexual and maternally motivated. Can she perceive the male as attractive and aversive, soliciting and attacking him at the same time? This study shows that postpartum estrous females exhibit a merge of sexual and maternal aggressive responses toward male intruders in the home cage. The concurrent expression of these behaviors did not affect their intensities, although the stimulation of maternal behavior increased maternal aggression without modifying sexual solicitation. These results indicate that the postpartum estrous rat can optimally express two opposite and independently regulated motivations, and that the male can be perceived as an ambivalent stimulus. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Sexual compulsivity, state affect, and sexual risk behavior in a daily diary study of gay and bisexual men.

Researchers have identified a strong link between sexual compulsivity (SC) and risky sexual behavior among men who have sex with men (MSM). Meanwhile, affect/mood has also been connected with negative sexual health outcomes (sexually transmitted infection/human immunodeficiency virus [HIV] transmission, sexual risk, sex under the influence of drugs/alcohol). Given that SC is characterized by marked distress around one's own sexual behavior, affect may play a central role in SC and HIV risk behavior. Data were taken from the Pillow Talk Project, a pilot study conducted in 2008–2009 with 50 highly sexually active MSM (9 or more male sex partners, ≤ 90 days), of which half displayed SC symptoms and half did not. Forty-seven men completed a daily diary online for 30 days (n = 1,060 diary days), reporting on their sexual behavior and concurrent affect: positive activation, negative activation, anxious arousal, and sexual activation. We conducted HLM analyses using daily affect (Level 1, within subjects) and SC and HIV status (Level 2, between subjects) to predict sexual behavior outcomes. Increased negative activation (characterized by fear, sadness, anger, and disgust) was associated with reduced sexual risk behavior, but less so among sexually compulsive MSM. Sexual activation was associated with increased sexual risk taking, but less so among sexually compulsive MSM. Anxious arousal was associated with increased sexual behavior, but not necessarily sexual risk taking. Findings indicate that affect plays key roles in sexual behavior and sexual risk taking; however, the association between affect and behavior may be different for sexually compulsive and non-sexually compulsive MSM. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Serotonin impairs copulation and attenuates ejaculation-induced glutamate activity in the medial preoptic area.

The medial preoptic area (MPOA) is critical for male sexual behavior. Glutamate is released in the MPOA of male rats during copulation, and increasing glutamate levels by reverse dialysis of glutamate uptake inhibitors facilitates mating. Conversely, increased release of serotonin (5-HT) inhibits sexual behavior. In both rats and men, selective serotonin reuptake inhibitors (SSRIs) impair erection, ejaculation, and libido. Here we reverse-dialyzed 5-HT through concentric microdialysis probes in the MPOA of male rats; concurrently we collected 2-min samples for analysis of glutamate and measured sexual behavior. Sexual activity, and especially ejaculation, increased levels of glutamate in the MPOA. However, reverse dialysis of 5-HT into the MPOA impaired ejaculatory ability and attenuated glutamate release. Implications of these results for impairment of sexual behavior that results from administration of SSRIs are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sexual Dimorphism and the NMDA Receptor in Alloparental Behavior in Juvenile Prairie Voles (Microtus ochrogaster).

The prairie vole (Microtus ochrogaster) exhibits parental behavior in both males and females and extensive alloparenting in juveniles. The authors studied the effects on juvenile alloparenting of antagonists for the PCP, glycine, and glutamate sites on the N-methyl-D-aspartate (NMDA) receptor. In male voles, all 3 drugs had an inverted-U dose-response curve. This change could not be attributed to fear of the pup or a nonspecific impairment of cognition, level of locomotor activity, or motor coordination. The PCP site antagonist had a U-shaped dose-response curve in females, the opposite of that in males, but neither of the other drugs changed female alloparental behavior. Both male and female voles exhibit alloparental behavior, but its neurobiological underpinnings are sexually dimorphic in juveniles. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Risk analysis of menstrual disorders in young women from urban population

The selective non-competitive N-methyl-D-aspartate (NMDA) antagonist (+)-5-methyl-10, 11-dihydro-5H-dibenzo(a, d)cyclohepten-5,10-imine maleate ((+)MK-801) led to a dose-dependent increase in locomotor activity in mice pretreated with a combination of reserpine and alpha-methyl-para-tyrosine (alpha-MT). A selective and potent sigma receptor "antagonist" NE-100 (N, N-dipropyl-2- [4-methoxy-3-(2-phenylethoxy)-phenyl]-ethylamine monohydrochloride), which did not per se affect spontaneous locomotor activity, did not prevent the locomotor stimulatory effects of (+)MK-801. Sulpiride, a dopamine D2 receptor antagonist, and clozapine, a dopamine D4 receptor antagonist, which decreased spontaneous locomotor activity, did not prevent the locomotor stimulatory effects of (+)MK-801. The sigma receptor "agonists" (+)N-allynormetazocine [(+)SKF10,047], (+)pentazocine and (+)-3-(3-hydroxyphenyl)-N-(1-propyl) piperidine [(+)3-PPP], which did not per se affect spontaneous locomotor activity, did dose-dependently enhance the hyperlocomotion induced by (+)MK-801. The enhancement of (+)MK-801-induced the hyperlocomotion by (+)SKF10,047, (+)pentazocine and (+)3-PPP was completely blocked by NE-100. The enhancement of (+)MK-801-induced hyperlocomotion by (+)pentazocine was not affected by treatment with sulpiride and clozapine. As sigma ligands can markedly attenuate NMDA antagonist-induced behavior, the major physiological role of sigma receptors in vivo might be to modulate functions of the NMDA receptor ion channel complex.     

NMDA receptors mediate peripheral chemoreceptor afferent input in the conscious rat

N-methyl-D-aspartate (NMDA) glutamate receptors mediate critical components of cardiorespiratory control in anesthetized animals. The role of NMDA receptors in the ventilatory responses to peripheral and central chemoreceptor stimulation was investigated in conscious, freely behaving rats. Minute ventilation (VE) responses to 10% O2, 5% CO2, and increasing intravenous doses of sodium cyanide were measured in intact rats before and after intravenous administration of the NMDA receptor antagonist MK-801 (3 mg/kg). After MK-801, eupcapnic tidal volume (VT) decreased while frequency increased, resulting in a modest reduction in VE. Inspiratory time (TI) decreased, whereas expiratory time remained unchanged. The VE responses to hypercapnia were qualitatively similar in control and MK-801 conditions, with slight reductions in respiratory drive (VT/TI) after MK-801. In contrast, responses to hypoxia were markedly attenuated after MK-801 and were primarily due to reduced frequency changes, whereas VT was unaffected. Sodium cyanide doses associated with significant VE increases were 5 and 50 microg/kg before and after MK-801, respectively. Thus 1-log shift to the right of individual dose-response curves occurred with MK-801. Selective carotid body denervation reduced VE during hypoxia by 70%, and residual hypoxic ventilatory responses were abolished after MK-801. These findings suggest that, in conscious rats, carotid and other peripheral chemoreceptor-mediated hypoxic ventilatory responses are critically dependent on NMDA receptor activation and that NMDA receptor mechanisms are only modestly involved during hypercapnia.     

Effects of pre- and postpubertal social experience on sexual and social behavior in male and female brown lemmings (Lemmus sibiricus).

In 3 studies, male and female brown lemmings were either isolated at weaning (18 days) or then housed with siblings for another 10 days before being isolated. Before testing for sexual behavior at the age of 75–103 days, half of each group of males received a series of exposures to estrous females and half of each group of females was housed with a stud male. The results of mating tests indicate that whereas prior sexual experience facilitated subsequent copulatory behavior in both sexes, prepubertal interactions subsequently facilitated contact social and sexual behavior in males but did not increase the behavioral scores of females, who engaged in high levels of sexual behavior regardless of prepubertal experience. The effect of prior copulatory activity on male sexual performance could not be attributed to increasing age (i.e., maturational processes) because the behavior of males tested once but at different ages did not differ appreciably. Prepubertal social interaction appeared to predispose males to benefit from sexual experience later in life. (35 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)