REDUCED LORDOSIS BEHAVIOR AFTER INTRACEREBRAL 8-OH-DPAT

这项研究的目的是了解5-羟色胺在 女性的性行为。PI之前的工作重点是 特异性5-羟色胺受体作用的神经部位鉴定 参与调节前凸反应的亚型。她有 确定VMN为5HT行动的地点，并已表明5HT1a和 5HT2A/2C受体亚型分别抑制和促进前凸。 目前的提案将继续这一调查路线，重点是 认为5-羟色胺对前凸有双重作用，这两种受体 亚型5HT1A和5HT2A/2C协同作用调节感受性。这个 Pi曾假设这是VMN中5HT1a位点的激活 在发情前期减弱，并激活5HT2A/2C受体 减弱5HT1a受体抑制前凸的作用。她有 从这一假设中得出了几个可检验的预测。其中一些 这些数据已经过测试，并已在初步数据中报告 一节。其他人构成了这项提案的主体。 修订后的申请有七个目标。前三个目标包括 检测不同的5HT1A和5HT2A/2C激动剂的作用 拮抗剂在激素诱导的卵巢切除大鼠中的作用 在这些双重5-羟色胺能效应的一般情况下。最后四个目标 旨在研究5HT1a受体 激动剂抑制前凸，5HT2A/2C激动剂促进前凸。这个 有待测试的两种机制是G蛋白偶联到腺酰环化酶 G蛋白偶联K+通道。这些选择基于报告 抑制腺酰环化酶的药物抑制前凸，而药物 这促进了磷脂酰肌醇系统促进前凸。

The goal of this research is to understand the role of serotonin in female sexual behavior. The PI's previous work has focussed on identification of neural sites for the action of specific 5HT receptor subtypes involved in the mediation of the lordosis response. She has identified the VMN as a site for 5HT action and has shown that 5HT1A and 5HT2A/2C receptor subtypes respectively inhibit and facilitate lordosis. The current proposal will continue this line of inquiry, focussing on the idea that 5HT has dual effects on lordosis, and that these two receptor subtypes, 5HT1A and 5HT2A/2C, act in concert to modulate receptivity. The PI has hypothesized that it is the activation of 5HT1A sites in the VMN that are attenuated on proestrus, and the 5HT2A/2C receptor activation attenuates the lordosis-inhibiting effects of 5HT1A receptors. She has developed several testable predictions from this hypothesis. Some of these have already been tested and are reported in the preliminary data section. The others make up the body of this proposal. The revised application has seven aims. The first three aims involve testing the effects of various 5HT1A and 5HT2A/2C agonists and antagonists in the suboptimally hormone-primed ovariectomized rat to get at the generality of these dual serotonergic effects. The last four aims are designed to investigate the mechanism by which 5HT1A receptor agonists inhibit lordosis and 5HT2A/2C agonists facilitate lordosis. The two mechanisms to be tested are G-protein coupling to adenylyl cyclase and G-protein coupling to K+ channels. These choices are based on reports that agents which inhibit adenylyl cyclase inhibit lordosis while agents which facilitate the phosphoinositide system facilitate lordosis.