The proposed research is designed to identify the CNS site(s) responsible for the inhibition of female rat sexual behavior after treatment with the 5-HT1A agonist, 8-hydroxy-2-9(di-n-propylamino) tetralin (8-OH-DPAT). Activation of somal/dendritic 5-HT1A autoreceptors by 8-OH-DPAT decreases the firing of 5-HT neurons and reduces the release of 5-HT in regions innervated by these neurons. In terminal fields, the 5-HT1A receptor exists at postsynaptic sites. Although it may also reside on presynaptic terminals, the 5-HT1A receptor does not function as the terminal autoreceptor.
The specific aims of the proposed studies are: (1) to identify the neural areas sufficient for the inhibition of female sexual behavior following treatment with 8-OH-DPAT and (2) to compare the effectiveness of this 5-HT1A agonist with that of other 5-HT1A agonists and 5-HT1B-preferring agonists. The effects of putative 5-HT1A antagonists will also be studied. Intact, regularly cycling female rats will be used and special emphasis will be placed on differentiating the postsynaptic effects of 8-OH-DPAT will then be infused intracerebrally into the medial basal hypothalamus and medial preoptic area, terminal fields that control female reproduction, and into the dorsal raphe nucleus, which contains 5-HT cell bodies. Sexual behavior will be monitored before and after infusion. These studies will provide the foundation for future investigations aimed at identifying the molecular nature and functional consequences of 5-HT1A- mediated control of sexual behavior.
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