This research will clarify how gonadal hormones influence neurotransmitter release in a key site for the control of male sexual behavior. The medial preoptic area (MPOA) is essential for males' copulation in virtually all vertebrate species. MPOA dopamine facilitates male rats' sexual motivation, copulatory motor patterns, and genital reflexes. (1) Nitric oxide, an unusual, gaseous messenger molecule, may regulate MPOA dopamine release. Histochemistry and microdialysis will be used to study hormonal influence on the enzyme that synthesizes nitric oxide. A nitric oxide donor drug will be administered via microdialysis, to test whether it restores dopamine release or copulation in castrates. (2) Testosterone may decrease activity of the enzyme that synthesizes dopamine. Castrated male rats become slower to initiate copulation, but if they do begin, they ejaculate sooner than intact males. The slower initiation may result from an excess of stored dopamine, which would facilitate ejaculation if it could be released. Immunocytochemistry will be used to study the influence of gonadal hormones on this enzyme in the MPOA. Microdialysis will be used to test whether high doses of anabolic steroids impair sexual behavior, in part, by excessive inhibition of MPOA dopamine synthesis. (3) It will also be used to study the means by which dioxin (TCDD, an environmental toxin), or an antipsychotic drug (haloperidol), administered prenatally, interfere with sex differentiation. Dopamine release will be measured in the MPOA of male rats in the presence of male or female partners. This research will provide important information about biological influences on sexual preference as well as impairments resulting from perinatal insults. (4) Lesions of the medial amygdala impair the ability to ejaculate. This research will test whether medial amygdala lesions reduce MPOA dopamine release before or during copulation. (5) Finally, this research will study the influence of MPOA serotonin on male sexual behavior. Serotonin generally inhibits sexual behavior, but one class of serotonergic drugs facilitate copulation. Microdialysis will be used to measure serotonin levels, to administer serotonergic drugs, and to determine the effects of serotonergic antidepressants on neurotransmitter release in the MPOA. These antidepressants frequently impair sexual function in humans.
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