REDUCED LORDOSIS BEHAVIOR AFTER INTRACEREBRAL 8-OH-DPAT

这项研究的目的是了解血清素的作用， 女性性行为PI以前的工作集中在 特异性5-HT受体作用的神经部位的鉴定 参与脊柱前凸反应调节的亚型。她有 将VMN确定为5 HT行动的地点，并表明5 HT 1A和 5 HT 2A/2C受体亚型分别抑制和促进脊柱前凸。 目前的建议将继续这一调查路线，重点是 认为5-HT对脊柱前凸有双重作用， 亚型5 HT 1A和5 HT 2A/2C协同作用以调节感受性。的 PI假设这是VMN中5 HT 1A位点的激活 在动情前期减弱，5 HT 2A/2C受体激活 减弱5 HT 1A受体的脊柱前凸抑制作用。她有 从这个假设中发展出几个可检验的预测。一些 这些已经过测试，并在初步数据中报告 科.其他人构成了本提案的主体。 修订后的应用程序有七个目标。前三个目标包括 测试各种5 HT 1A和5 HT 2A/2C激动剂的作用， 拮抗剂在次最佳预处理的卵巢切除大鼠中， 在这些双重的多巴胺能效应的一般性。最后四个目标 目的是研究5 HT 1A受体 激动剂抑制脊柱前凸，5 HT 2A/2C激动剂促进脊柱前凸。的 两种待测试的机制是G蛋白偶联腺苷酸环化酶 和G蛋白偶联到K+通道。这些选择是基于报告 抑制腺苷酸环化酶的药物抑制脊柱前凸，而抑制腺苷酸环化酶的药物 其促进磷酸肌醇系统促进脊柱前凸。

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.