The objective of proposed studies is to determine how the gonadal hormone estradiol interacts within the central nervous system to regulate reproductive function. Experiments will specifically evaluate whether hormone dependent changes in the serotonergic system contribute to the facilitation of feminine sexual behavior, the lordosis response. Gonadal hormones will be administered to ovariectomized rats in doses which are just sufficient to activate behavior, and effects on serotonergic activity and activity of monomine oxidase (MAO, enzyme which degrades serotonin), will be assessed in behaviorally relevant hypothalamic nuclei. Identical experiments in castrate males will determine whether the neurochemical response, like the behavioral, is sexually dimorphic. Measurement of these neurochemical parameters as well as circulating hormones and behavior on proestrus day of the estrus cycle will determine whether the observed changes in serotonin and MAO are consistent with the time of facilitated lordosis. The serotonergic toxin, 5,7-dihydroxytryptamine, will also be utilized to explore fundamental questions of how hormones activate behavior and whether sexual differentiation of serotonin containing neurons contributes to the dimorphic expression of behavior. Thus, the experiments should determine whether serotonergic regulation of lordosis is pharmacologic or physiologic, provide information on themechanisms whereby serotonin regulates lordosis, and whether sexual differentiation of serotonin contributes to dimorphic expression of behavior. Information concerning the mechanism of gonadal hormone regulation of brain function may be valuable in treatment of diseases affecting neuroendocrine functions. In addition, some drugs to be used are commonly used for management of affective disorders. Information regarding their mechanism of action and untoward reactions with hormone dependent processes will be obtained.
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