Reduced Lordosis Behavior after Intracerebral 8-OH-DPAT

描述（由申请人提供）：在内侧基底下丘脑（MBH）内，5-羟色胺（5-HT）可抑制和促进雌性大鼠的性感受性。我们认为，这种双重调节是重要的，允许女性协调她的生殖行为与外部环境。即使雌性是最佳的性接受能力，在生命受到威胁的情况下，交配对雌性来说也是一个不恰当的行为选择。然而，如果这种威胁是最小的，增加对压力的脆弱性可能会不必要地减少生殖成功。我们的重点是5-HT 1A，5-HT 2C和5-HT 1B受体之间的相互作用。我们的工作模型是，轻度应激（5分钟限制）增加释放的5-HT在MBH。增加的细胞外5-HT激活5-HT 1A、5-HT 1B和5-HT 2C受体。5-HT 1A受体的激活导致脊柱前凸行为的抑制，而5-HT 2C受体的激活限制了这种抑制的持续时间并允许恢复发生。孕酮增强末端5-HT 1B自身受体的功能，使得细胞外5-HT响应于应激而发生较小的增加。结果，5-HT 1A受体的占据不足以抑制脊柱前凸行为。所提出的实验旨在测试所提出的模型的每个元素。虽然拟议的研究集中在5-HT受体亚型在脊柱前凸行为的控制中的作用，但它们可以提供有关5-HT功能的激素调节以及这些激素如何影响女性对急性环境挑战的反应的有价值的信息。

DESCRIPTION (provided by applicant): Within the medial basal hypothalamus (MBH), serotonin (5-HT) can both inhibit and facilitate female rat sexual receptivity. We have suggested that this dual regulation is important in allowing the female to coordinate her reproductive behavior with the external environment. Even if the female were optimally sexually receptive, under life-threatening conditions, mating would be an inappropriate behavioral choice for the female to make. However, should the threat be minimal, increased vulnerability to stress might unnecessarily reduce reproductive success. Our emphasis is on the interplay among 5-HT1A, 5-HT2C and 5-HT1B receptors. Our working model is that mild stress (5 min restraint) increases the release of 5-HT in the MBH. The increased extracellular 5-HT activates 5-HT1A, 5-HT1B and, 5-HT2C receptors. Activation of 5-HT1A receptors leads to inhibition of lordosis behavior while activation of 5-HT2C receptors limits the duration of this inhibition and allows recovery to occur. Progesterone enhances the function of terminal 5-HT1B autoreceptors so that a smaller increase in extracellular 5-HT occurs in response to stress. As a result, the occupation of 5-HT1A receptors is insufficient for inhibition of lordosis behavior. The proposed experiments are designed to test each element of this proposed model. Although the proposed studies are focused on the role of 5-HT receptor subtypes in the control of lordosis behavior, they can provide valuable information about hormonal modulation of 5-HT function and how these hormones influence the female's response to an acute environmental challenge.