The long term objectives of experiments are to understand the mechanisms responsible for gonadal hormone interactions in the CNS during development and in adulthood to promote reproductive function. Experiments are focused specifically on contributions of the neurotransmitter serotonin (5HT) to the regulation of female sexual behavior, lordosis. Previous grant periods have shown that alterations in this system are critical for the hormonal activation of lordosis and that this system shows robust differences between males and females in its sensitivity and response to gonadal hormones. Proposed experiments, utilizing primarily neurochemical techniques, will assess the activity of 5HT and related neurochemicals during proestrus in specific hypothalamic sites which are known to regulate lordosis and where gonadal hormone treatments lead to alterations in 5HT function. In vivo dialysis techniques will be implemented to further assess serotonergic and catecholaminergic function in hypothalamic sites after gonadal hormone administration, during the estrous cycle and after drug treatments. Whether GABA containing neurons in the hypothalamus serve as the mediators of gonadal hormone effects on serotonergic endings will be investigated. GABAergic drugs will be applied to the hypothalamus and effects on lordosis measured. Gonadal hormone effects on GABA activity and effects of GABAergic drugs on 5HT activity will be measured. The understanding of mechanisms for gonadal hormone regulation of brain function may be valuable for treatment of neuroendocrine problems such as infertility and spontaneous abortion in women, and psychosexual and impotency problems in men. Knowledge of serotonergic function within this neuroendocrine context may also provide information relevant for understanding how serotonergic systems exert effects on appetite, circadian rhythmicity, depression and anxiety states.
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