The long-term objective of this research is to establish how hormonal signals are recognized by brain cells and subsequently translated into specific changes in behavior. To accomplish this goal, studies are focused on elucidating the mechanisms by which the ovarian steroid hormones regulate the expression of one component of female reproductive behavior, the lordosis response. Previous work has provided evidence that estrogenic facilitation of lordosis involves receptor-mediated regulation of gene expression in neurons of the ventromedial hypothalamus (VMH). The research described in this proposal uses a combination of behavioral and biochemical techniques to test the hypothesis that ovarian steroid induction of lordosis in female rats is mediated by augmentation of norepinephrine (NE) transmission in or near the VMH. Specific experiments will ask: (1) Does steroid activation of lordosis behavior require NE transmission in or near the VMH? If so, which NE receptor subtype(s) mediate the effects of NE on lordosis? (2) Do hormone treatments which facilitate lordosis behavior augment basal and/or evoked release of NE in or near the VMH? (3) Are the facilitatory and inhibitory effects of other neurotransmitters and neuromodulators on steroid-dependent lordosis mediated by alterations in NE release in or near the VMH? (4) Are sex differences in steroid facilitation of lordosis responsiveness due to sex differences in hormonal regulation of NE transmission in or near the VMH? (5) Do ovarian steroids regulate activity of tyrosine hydroxylase, the rate-limiting enzyme in NE synthesis, in or near the VMH? If so, are soluble and/or synaptosomal tyrosine hydroxylase the target of regulation, and what is the mechanism of regulation? The new information provided by these studies will form the foundation for future work, the ultimate goal of which is to define the precise molecular mechanisms by which hormones act in brain tissue to bring about specific behavioral changes. Clarification of the effects of ovarian steroids on NE transmission in the brain may allow us to develop testable hypotheses regarding the relationships among hormones, premenstrual complaints, postmenopausal complaints, stress, depression and anxiety. In addition, studies on sex differences in neurotransmitter regulation might yield insight into sex differences in the occurrence of psychiatric illnesses and the neural responses to therapeutic agents, such as antidepressants.
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