Dopamine In Medial Preoptic Area Research Articles

Sex, drugs and gluttony: How the brain controls motivated behaviors

Bart Hoebel has forged a view of an integrated neural network that mediates both natural rewards and drug use. He pioneered the use of microdialysis, and also effectively used electrical stimulation, lesions, microinjections, and immunohistochemistry. He found that feeding, stimulant drug administration, and electrical stimulation of the lateral hypothalamus (LH) all increased dopamine (DA) release in the nucleus accumbens (NAc). However, whereas DA in the NAc enhanced motivation, DA in the LH inhibited motivated behaviors. The Hull lab has pursued some of those ideas. We have suggested that serotonin (5-HT) in the perifornical LH inhibits sexual behavior by inhibiting orexin/hypocretin neurons (OX/HCRT), which would otherwise excite neurons in the mesocorticolimbic DA tract. We have shown that DA release in the medial preoptic area (MPOA) is very important for male sexual behavior, and that testosterone, glutamate, nitric oxide (NO) and previous sexual experience promote MPOA DA release and mating. Future research should follow Bart Hoebel's emphasis on neural systems and interactions among brain areas and neurotransmitters.

The effects of nitric oxide–cGMP pathway stimulation on dopamine in the medial preoptic area and copulation in DHT-treated castrated male rats

Dopamine (DA) in the medial preoptic area (MPOA) provides important facilitative influence on male rat copulation. We have shown that the nitric oxide–cGMP (NO–cGMP) pathway modulates MPOA DA levels and copulation. We have also shown that systemic estradiol (E 2) maintains neuronal NO synthase (nNOS) immunoreactivity in the MPOA of castrates, as well as relatively normal DA levels. This effect of E 2 on nNOS probably accounts for at least some of the previously demonstrated behavioral facilitation by intra-MPOA E 2 administration in castrates. Therefore, we hypothesized that stimulation of the MPOA NO–cGMP pathway in dihydrotestosterone (DHT)-treated castrates should restore DA levels and copulatory behaviors. Reverse-dialysis of a NO donor, sodium nitroprusside (SNP), increased extracellular DA in the MPOA of DHT-treated castrates and restored the ability to copulate to ejaculation in half of the animals. A cGMP analog, 8-Br-cGMP, also increased extracellular DA, though not as robustly, but did not restore copulatory ability. The effectiveness of the NO donor in restoring copulation and MPOA DA levels is consistent with our hypothesis. However, the lack of behavioral effects of 8-Br-cGMP, despite its increase in MPOA DA, suggests that NO may have additional mediators in the MPOA in the regulation of copulation. Furthermore, the suboptimal copulation seen in the NO donor-treated animals suggests the importance of extra-MPOA systems in the regulation of copulation.

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.

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 17β-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.

Chemosensory Cues are Essential for Mating-Induced Dopamine Release in MPOA of Male Syrian Hamsters

The medial preoptic area (MPOA) is crucial for male sex behavior. Dopamine (DA) is released in MPOA during copulation, and contributes to the reinforcing effects of mating. The aim of the present study was to identify sensory stimuli responsible for mating-induced DA release. Specifically, we determined if chemosensory cues are essential for mating-induced MPOA DA release using in vivo microdialysis in male Syrian hamsters. Hamsters were used because chemosensory cues from the olfactory mucosa and vomeronasal organ are essential for sexual behavior in this species. Sexually experienced adult male hamsters were implanted with a microdialysis guide cannula over MPOA. At the same time, males received sham olfactory bulbectomy (Sham Bx, n = 11), bilateral bulbectomy (Bibx, n = 6), or unilateral bulbectomy (Ubx) ipsilateral (Ipsi Ubx, n = 9) or contralateral (Contra Ubx, n = 8) to the microdialysis probe. This model takes advantage of the predominantly ipsilateral projections of the olfactory bulbs. Microdialysis samples were collected from the MPOA during baseline, exposure to a receptive female, and after removal of female. Extracellular DA was measured using high-performance liquid chromatography with electrochemical detection. During mating, DA increased in MPOA of Sham Bx males (to 146.7 +/- 17.5% of baseline). Bibx males did not mate, and MPOA DA did not increase (96.1 +/- 15.8% of baseline). Although both groups of Ubx males mated to ejaculation, MPOA DA increased significantly only in Contra Ubx males (to 161.8 +/- 35.3% of baseline), and not in males with Ipsi Ubx (107.6 +/- 11.5% of baseline). The results demonstrate that chemosensory cues are essential for MPOA DA release during mating in male Syrian hamsters.

Stimulation of the medial amygdala enhances medial preoptic dopamine release: implications for male rat sexual behavior

Increased dopamine (DA) in the medial preoptic area (MPOA) facilitates male sexual behavior. A major source of innervation to the MPOA is the medial amygdala (MeA). We now report that chemical stimulation of the MeA enhanced levels of extracellular MPOA DA in anesthetized male rats. These results suggest that DA activity in the MPOA can be regulated by input from the MeA to the MPOA.

Testosterone Restoration of Copulatory Behavior Correlates with Medial Preoptic Dopamine Release in Castrated Male Rats

The medial preoptic area (MPOA) is an important integrative site for male sexual behavior. We have reported an increase in dopamine (DA) release in the MPOA of male rats shortly before and during copulation. Postcastration loss of copulatory ability mirrored the loss of the precopulatory DA response to an estrous female. The present study investigated the time courses of restoration, rather than loss, of the MPOA DA response to a receptive female and of copulation in long-term castrates. Male rats were castrated and tested for loss of copulatory ability 21 days later. They then received 2, 5, or 10 daily subcutaneous injections of testosterone propionate (TP, 500 μg) or oil. Microdialysate samples were collected from the MPOA during baseline, exposure to a female behind a barrier, and copulation. Extracellular DA was measured using HPLC–EC. None of the six 2-day-TP-treated animals copulated, nor did they show elevated DA release in the MPOA in the presence of a receptive female. Five of the nine 5-day-TP-treated animals ejaculated; three intromitted without ejaculating; and one failed to copulate, with all but the noncopulating animal showing elevated DA release. All of the six 10-day-TP-treated animals copulated and also demonstrated an increase in MPOA DA. None of the oil controls copulated or showed an increase in DA release. Therefore, a consistent relationship between MPOA DA release during exposure to a receptive female and the subsequent ability of the male to copulate was observed.

Regulation by the Medial Amygdala of Copulation and Medial Preoptic Dopamine Release

The medial preoptic area (MPOA) is a critical integrative site for male copulatory behavior in most vertebrate species. Extracellular dopamine (DA) is increased in the MPOA of male rats immediately before and during copulation. DA agonists microinjected into the MPOA of male rats facilitate and DA antagonists inhibit sexual behavior. A major source of input to the MPOA is the medial amygdala (MeA), which processes and relays olfactory information to the MPOA. We now report that microinjections of a DA agonist into the MPOA of animals with excitotoxic lesions of the amygdala restored copulatory ability that was lost after the lesions. Moreover, radio-frequency lesions of the MeA impaired copulation and blocked the increases in extracellular DA seen in animals with sham lesions during exposure to a receptive female and during copulation. Thus, both copulatory ability and the MPOA DA response, during exposure to a receptive female and during copulation, are facilitated by input from the MeA to the MPOA.

Castration decreases extracellular, but increases intracellular, dopamine in medial preoptic area of male rats

Dopamine (DA) is released in the medial preoptic area (MPOA) of male rats in the presence of a female, and it facilitates male sexual behavior. Castration blocks the DA response to a female and the male's ability to copulate. The present experiments examined the effects of castration on (1) basal levels of extracellular DA in the MPOA, using the no net flux microdialysis technique, (2) the response of extracellular DA to amphetamine, and (3) tissue levels of DA. Castrated rats had lower basal levels of extracellular DA in the MPOA, compared with gonadally intact rats; in vivo recovery, a measure of uptake, was not different. This suggests that castration decreases DA release in basal conditions, as well as in response to a female. However, systemic amphetamine injections, which induce DA release, resulted in greater DA release in castrates. Finally, tissue levels of DA were higher in the MPOA, the caudate–putamen and the bed nucleus of stria terminalis of castrates. These data suggest that DA synthesis and storage in the MPOA are normal, or even enhanced, in castrates, and uptake is not altered. The deficit in extracellular levels appears to be related to release, perhaps due to decreased nitric oxide.

Copulation increases dopamine activity in the medial preoptic area of male rats

Dopamine (DA) metabolites in microdialysates from the medial preoptic area (MPOA) of male rats increased during copulation. These increases were not observed during eating of a highly palatable food, or if the animal failed to copulate, or if the microdialysis probe was anterior or dorsal to the MPOA. The only two animals with measurable serotonin (5-HT) levels while the female was present were also the only two that either failed to copulate or copulated but failed to ejaculate. These data are consistent with previous evidence for a facilitative role of MPOA DA in the control of male sexual behavior; however, 5-HT activity in the MPOA may impair copulation.

Sexual refractoriness and locomotion effects on brain monoamines in the male rat

Serotonin (5-HT), 5-hydroxyindolacetic acid (5-HIAA), dopamine (DA), dihydroxyphenylacetic acid (DOPAC), and norepinephrine (NE) concentrations in seven brain regions were compared in sexually refractory, physically active, and inactive male rats. Also examined were 5-HIAA/5-HT and DOPAC/DA concentration ratios. Sexually refractory males were permitted uninterrupted copulation with successive receptive females until they failed to mount or ejaculate in a set period. Physically active males ran in motor-driven activity wheels except during the postejaculatory refractory periods of experimental animals, and inactive males remained alone in testing arenas. Significant group differences were found only in monoamine concentrations in the medial preoptic area (MPOA) and the medial forebrain bundle (MFB). In the MPOA, 5-HT concentration was elevated in sexually refractory males, as was DA in both refractory and active animals. In the MFB, 5-HT concentration was increased in active males. MFB DOPAC levels of sexually refractory rats significantly correlated inversely with their ejaculation totals, as did MFB and dorsal raphe (DR) NE levels. The results suggest that the MPOA is a forebrain target for inhibitory influences on male rat sexual behavior of ascending serotonergic fibers and that increased MFB 5-HT and MPOA DA may be associated with general activity.