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Elaine M Hull

Publications and source records attributed to Elaine M Hull.

13 recordsLinked to original sources
PubMed2006

Getting his act together: roles of glutamate, nitric oxide, and dopamine in the medial preoptic area.

Gonadal hormones have primarily slow, genomically mediated effects, but copulation requires rapid interactions with a partner. A major way in which hormones facilitate male sexual behavior is by increasing production of neurotransmitter receptors or of enzymes that regulate neurotransmitter synthesis or release. Dopamine is an important facilitative neurotransmitter, and the medial preoptic area (MPOA) is a critical integrative site for male sexual behavior. MPOA dopamine is released before and during mating and facilitates copulation, genital reflexes, and sexual motivation. Gonadal hormones regulate dopamine release in the MPOA of male rats in part by increasing nitric oxide synthase (NOS) in the MPOA; the resultant increase in production of nitric oxide (NO) increases both basal and female-stimulated dopamine release. Glutamate also increases dopamine release via increased production of NO. At least some of the glutamatergic inputs to the MPOA are from the medial amygdala (MeA) and bed nucleus of the stria terminalis (BNST), which mediate the female-stimulated increase in dopamine, which in turn enhances copulatory ability. Extracellular glutamate in the MPOA increases during copulation, especially during ejaculation, and increased glutamate facilitates copulation and genital reflexes. Previous sexual experience also facilitates copulation and confers resistance to impairment by various lesions, drugs, and stress. Experience enhances processing of sexual stimuli, and its effects require activation of glutamate NMDA receptors and NOS in the MPOA. Neuronal NOS is increased in the MPOA of experienced males. Therefore, glutamate, NO, and dopamine interact in the MPOA to facilitate mating and to enhance future sexual responsiveness.

Animals↗
PubMed2006

Preoptic glutamate facilitates male sexual behavior.

The medial preoptic area (MPOA) is a critical regulatory site for the control of male sexual behavior. We first measured glutamate in 2 min microdialysate samples from the MPOA before, during, and after copulation by male rats. There was a slight [approximately 140% of baseline (BL)] rise in extracellular glutamate when the female was presented, a significant increase (approximately 170% of BL) during periods of mounting and intromitting, and a very large increase in samples collected during ejaculation (approximately 300% of BL). A precipitous fall in levels occurred in the first postejaculatory sample; the magnitude of this fall was highly correlated with the length of the postejaculatory interval of quiescence. In experiment 2, we reverse-dialyzed a mixture of glutamate uptake inhibitors into the MPOA before and during mating; control animals received artificial CSF. The mixture increased extracellular glutamate (approximately 280% of BL), increased the number of ejaculations in the 40 min test, decreased ejaculation latency, and decreased the postejaculatory latency to resume copulation. These data, together with other findings that glutamate in the MPOA can elicit genital reflexes in anesthetized rats and that glutamate receptor antagonists in the MPOA impair copulation, strongly suggest that MPOA glutamate is a major facilitator of copulation and that the postejaculatory fall in glutamate regulates the postejaculatory interval.

Animals↗
PubMed2006

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.

Analysis of Variance↗
PubMed2005

Dopamine, the medial preoptic area, and male sexual behavior.

The medial preoptic area (MPOA), at the rostral end of the hypothalamus, is important for the regulation of male sexual behavior. Results showing that male sexual behavior is impaired following MPOA lesions and enhanced with MPOA stimulation support this conclusion. The neurotransmitter dopamine (DA) facilitates male sexual behavior in all studied species, including rodents and humans. Here, we review data indicating that the MPOA is one site where DA may act to regulate male sexual behavior. DA agonists microinjected into the MPOA facilitate sexual behavior, whereas DA antagonists impair copulation, genital reflexes, and sexual motivation. Moreover, microdialysis experiments showed increased release of DA in the MPOA as a result of precopulatory exposure to an estrous female and during copulation. DA may remove tonic inhibition in the MPOA, thereby enhancing sensorimotor integration, and also coordinate autonomic influences on genital reflexes. In addition to sensory stimulation, other factors influence the release of DA in the MPOA, including testosterone, nitric oxide, and glutamate. Here we summarize and interpret these data.

Animals↗
PubMed2005

Neuronal nitric oxide synthase and gonadal steroid interaction in the MPOA of male rats: co-localization and testosterone-induced restoration of copulation and nNOS-immunoreactivity.

Neuronal nitric oxide synthase (nNOS) in the medial preoptic area (MPOA) has been implicated in various physiological functions, including male rat copulation. Based on their apparent sensitivity to gonadal steroid manipulation, we hypothesized that nNOS cells contain steroid receptors, and the testosterone-induced restoration of nNOS-immunoreactivity in castrates should accompany the restoration of copulation. In Experiment 1, we investigated co-localization of nNOS with the androgen receptor (AR) and the estrogen receptor alpha (ERalpha) using immunocytochemistry. We found regionally specific co-localizations of nNOS-AR and nNOS-ERalpha. In Experiment 2, we investigated the relationship between MPOA nNOS-immunoreactivity (ir) and copulatory measures in the testosterone-induced restoration paradigm in castrates. The restoration of various copulatory measures was accompanied by an increase in optical density of nNOS-ir, but not in the number of nNOS-ir cells. These data provide additional evidence supporting the role of MPOA nitric oxide in male rat copulation.

Androgens↗
PubMed2005

Effects of testosterone metabolites on copulation, medial preoptic dopamine, and NOS-immunoreactivity in castrated male rats.

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. In a previous study, we identified 17beta-estradiol (E(2)) as the metabolite of testosterone (T) that maintains MPOA basal extracellular DA levels. However, the presence of dihydrotestosterone (DHT), an androgenic metabolite of T, is required for the female-induced increase in MPOA DA observed during copulation. Recently, we reported that assays of MPOA tissue DA content showed that castrates actually had more stored DA than did gonadally intact males. Therefore, the reduction in extracellular levels in castrates was not due to decreased availability of DA; most likely it was due to decreased release. Furthermore, T upregulates neuronal nitric oxide synthase (nNOS) in the MPOA. NO has been implicated in the regulation of DA release in the MPOA. It is not known, however, which metabolite(s) of T regulate(s) tissue stores of DA and/or nNOS in the MPOA of male rats. The present experiments were designed to test the following: (1) whether E(2), DHT, or the combination of the two influences MPOA DA tissue levels, an indication of stored DA, in male rat castrates; and (2) whether E(2), DHT, or the combination of the two influences NOS-ir in the MPOA of castrated male rats. The results indicate that E(2) up-regulates nNOS-ir in the MPOA and maintains tissue content of DA at levels similar to those in T-treated rats. DHT did not influence nNOS-ir, while attenuating the effect of castration on tissue DA content.

Analysis of Variance↗
PubMed2004

Dopamine and serotonin: influences on male sexual behavior.

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.

Animals↗
PubMed2004

Lysergic acid diethylamide and [-]-2,5-dimethoxy-4-methylamphetamine increase extracellular glutamate in rat prefrontal cortex.

The ability of hallucinogens to increase extracellular glutamate in the prefrontal cortex (PFC) was assessed by in vivo microdialysis. The hallucinogen lysergic acid diethylamide (LSD; 0.1 mg/kg, i.p.) caused a time-dependent increase in PFC glutamate that was blocked by the 5-HT(2A) antagonist M100907 (0.05 mg/kg, i.p.). Similarly, the 5-HT(2A/C) agonist [-]-2,5-dimethoxy-4-methylamphetamine (DOM; 0.6 mg/kg, i.p.), which is a phenethylamine hallucinogen, increased glutamate to 206% above saline-treated controls. When LSD (10 microM) was directly applied to the PFC by reverse dialysis, a rapid increase in PFC glutamate levels was observed. Glutamate levels in the PFC remained elevated after the drug infusion was discontinued. These data provide direct evidence in vivo for the hypothesis that an enhanced release of glutamate is a common mechanism in the action of hallucinogens.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed2004

A nitric oxide synthesis inhibitor in the medial preoptic area inhibits copulation and stimulus sensitization in male rats.

Dopamine in the medial preoptic area (MPOA) facilitates copulation in male rats, and nitric oxide (NO) regulates basal and female-stimulated MPOA dopamine release. Microinjection of L-nitro-arginine methyl ester (L-NAME, an NO synthesis inhibitor) into the MPOA blocked copulation in naive rats and impaired copulation in sexually experienced males. In other naive rats, L-NAME or saline was microinjected into the MPOA before each of 7 daily exposures to a receptive female placed over their cage. In a drug-free test on Day 8, copulation by L-NAME-treated rats was similar to that of unexposed controls and was impaired relative to saline-treated males. Therefore, NO in the MPOA is important for copulation and stimulus sensitization in male rats.

Analysis of Variance↗
PubMed2004

Women's orgasm.

An orgasm in the human female is a variable, transient peak sensation of intense pleasure, creating an altered state of consciousness, usually with an initiation accompanied by involuntary, rhythmic contractions of the pelvic striated circumvaginal musculature, often with concomitant uterine and anal contractions, and myotonia that resolves the sexually induced vasocongestion and myotonia, generally with an induction of well-being and contentment. Women's orgasms can be induced by erotic stimulation of a variety of genital and nongenital sites. As of yet, no definitive explanations for what triggers orgasm have emerged. Studies of brain imaging indicate increased activation at orgasm, compared to pre-orgasm, in the paraventricular nucleus of the hypothalamus, periaqueductal gray of the midbrain, hippocampus, and the cerebellum. Psychosocial factors commonly discussed in relation to female orgasmic ability include age, education, social class, religion, personality, and relationship issues. Findings from surveys and clinical reports suggest that orgasm problems are the second most frequently reported sexual problems in women. Cognitive-behavioral therapy for anorgasmia focuses on promoting changes in attitudes and sexually relevant thoughts, decreasing anxiety, and increasing orgasmic ability and satisfaction. To date there are no pharmacological agents proven to be beneficial beyond placebo in enhancing orgasmic function in women.

Arousal↗
PubMed2003

Effects of testosterone metabolites on copulation and medial preoptic dopamine release in castrated male rats.

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.

Analysis of Variance↗
PubMed2003

An NMDA antagonist impairs copulation and the experience-induced enhancement of male sexual behavior in the rat.

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.

Animals↗