This research will clarify the influence of gonadal hormones on 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 (DA) facilitates male rats' sexual motivation, copulatory motor patterns, and genital reflexes.
Aim 1 will investigate the factors that regulate DA release in the MPOA. Castrates have more intracellular, but less extracellular, DA in the MPOA than do intact males. A decrease in the soluble gas nitric oxide (NO) may contribute to the failure of castrates to release DA. In castrates, we will test the effects of the two major metabolites of testosterone, applied to the MPOA, on MPOA DA release and on the enzyme that synthesizes NO. We will also study the effects of sexual experience on DA release and behavior, determine the second messenger by which NO stimulates DA release, and study the interactions among DA, glutamate, and GABA in the MPOA.
Aim 2 will study the role of a major input to the MPOA. We will test whether lesions or stimulation of the medial amygdala influences DA or amino acid release in the MPOA.
Aim 3 will investigate the ability of DA to activate steroid receptors in a ligand-independent fashion, and thereby facilitate copulation, in male rats, as it does in females. We will test whether antisense oligonucleotides to progesterone, androgen, or estrogen receptors block the facilitative effects of a DA agonist release in the anterior lateral hypothalamus (LHA) at the time of ejaculation; a selective serotonin reuptake inhibitor (SSRI) injected there delays the onset of copulation and inhibits ejaculation. We will determine the receptor subtype(s) that mediate the inhibitory effects of 5-HT in the LHA. We will also measure basal and female-stimulated levels of 5-HT and DA in the LHA and the mesolimbic system after chronic treatment with an SSRI. SSRI antidepressants frequently impair sexual function in humans. This research should lead to better treatment for primary and SSRI-induced sexual dysfunctions. The teaching reduction provided by this award will allow me to learn to synthesize and use antisense oligonucleotides and to expand our use of microdialysis to detect amino acid neurotransmitters and of electrical stimulation to study functional circuits. It will also allow me to become more active in national and international scientific organizations.
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