Dopamine (DA) is released in the medial preoptic area (MPOA) of male rats in the presence of a receptive female, and it facilitates their copulation. Precopulatory DA release is highly predictive of copulatory ability. Testosterone (T) increases basal and female-stimulated DA release by up-regulating nitric oxide synthase (NOS), which produces nitric oxide (NO), which in turn increases DA release. We will now determine the hormonal and cellular factors that regulate DA release in the MPOA and will also determine the consequences of MPOA DA release on amino acid neurotransmitters. Aim 1 will determine whether T metabolites applied directly to the MPOA can maintain copulation, DA release, NOS immunoreactivity and DA receptors. We will also test whether androgen receptor-containing neurons in the MPOA are also immunoreactive for subtypes of DA receptors and whether castration affects those receptors. Aim 2 will determine the cellular factors that regulate the release of dopamine in the MPOA and the immediate consequences of DA release. Interactions with cGMP, glutamate, and GABA will be studied with both microdialysis and immunocytochemistry. Aim 3 will test mechanism(s) by which sexual experience may facilitate copulation. We will test whether basal or female-stimulated MPOA DA levels are higher in experienced than in naive males and whether injection of an NMDA antagonist into the MPOA prevents the facilitative effects of repeated exposures to a female. Aim 4 will determine the nature and functional significance of a major input to the MPOA. Lesions of the medial amygdala (MeA) blocked the MPOA DA response to a female and impaired copulation. Microinjection of a DA agonist into the MPOA restored copulatory ability in males with MeA lesions. We will now test whether electrical stimulation of the MeA increases DA, glutamate, and/or GABA release in the MPOA and whether axons from the MeA end near MPOA neurons that are immunoreactive for glutamate or GABA receptors or NOS. Two major clinical treatments for erectile disorder either prolong NO's peripheral and central effects or stimulate DA receptors; however, both have undesirable side effects. This research may lead to better treatments for sexual dysfunctions with fewer side effects.