Dopaminergic drugs are used to treat impotence; however, their side effects make current treatments less than ideal. This research will provide insights into mechanisms controlling sexual desire, erection, ejaculation, and somatomotor patterns, and should contribute to more specific treatment for sexual dysfunctions. In addition, it will provide insights into several basic issues: how hormones facilitate behavior; how the recently discovered messenger molecule, nitric oxide, may affect neurotramitter release and thereby contribute to sexual behavior; how sexual experience results in long term neural and behavioral changes; and how two major integrative systems interact to enhance sexual behavior. This work presents a conceptual model of three integrative systems that control motivated behaviors. It focuses on one of those integrative hubs, the medial preoptic area (MPOA). This brain area is critical for male sexual behavior in all vertebrate species that have been tested. Dopamine released in the MPOA of male rats during copulation facilitates sexual behavior. The proposed research addresses some of the specific causes and consequences of that dopamine release. 1. What internal factors regulate release of dopamine in the MPOA? The first experiments will test effectiveness of testosterone and of nitric oxide in enhancing dopamine release in the presence of a receptive female. Microdialysis will be used to measure transmitter release in the MPOA of castrates before and after testosterone replacement. Microdialysis will also be used to administer drugs affecting nitric oxide synthesis, and to measure transmitter release in the same area. Drugs diffuse out of, and transmitters diffuse into, the dialysis medium circulating through the dialysis probe. Transmitters will be assayed using HPLC with electrochemical detection. In addition, transmitter release in the presence of a receptive female will be compared in sexually experienced and naive male rats. 2. Are there long term effects of copulation-induced dopamine activity? Synaptic activity may lead to long term neural and behavioral changes by activating certain genes. Copulation activates one such gene, c-fos, in several sites including the MPOA. We will test whether blocking one subtype of dopamine receptor (D1) will block the c-fos expression, and/or the enhancement of copulatory efficient produced by sexual experience. 3. Does dopamine activity in the MPOA affect activity in the mesolimbic system? The MPOA may enhance sexual motivation by facilitating dopamine release in the mesolimbic system, which is thought to increase general activation. Changes in dopamine release in the mesolimbic system, produced by stimulating or blocking dopamine receptors in the MPOA, will be measured. This will test whether the MPOA may increase sexual motivation by activating the mesolimbic system.
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