Reduced Lordosis Behavior after Intracerebral 8-OH-DPAT

描述(申请人提供)：在下丘脑内侧基底(MBH)，5-羟色胺(5-HT)既能抑制也能促进雌性大鼠性感受性。我们认为，这种双重调节在允许雌性与外部环境协调其生殖行为方面是重要的。即使雌性在危及生命的情况下具有最佳的性接受性，交配也是雌性做出的不恰当的行为选择。然而，如果威胁微乎其微，更容易受到压力的影响可能会不必要地降低生育成功率。我们的重点是5-HT1A、5-HT2C和5-HT1B受体之间的相互作用。我们的工作模型是，轻度应激(束缚5分钟)会增加MBH中5-羟色胺的释放。细胞外5-羟色胺的增加激活了5-HT1A、5-HT1B和5-HT2C受体。5-HT1a受体的激活导致前凸行为的抑制，而5-HT2C受体的激活限制了这种抑制的持续时间，并允许恢复。孕酮增强了5-HT1B末端自身受体的功能，因此细胞外5-羟色胺在应激反应中的增加较少。因此，5-HT1a受体的占位不足以抑制前凸行为。建议的实验旨在测试该建议模型的每个元素。虽然所提出的研究集中在5-羟色胺受体亚型在控制前凸行为中的作用，但它们可以提供关于激素对5-羟色胺功能的调节以及这些激素如何影响雌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.