Progestins' non-genomic actions for socio-sexual behavior

孕酮(P)调节探索、焦虑、社会和性(社会-性)行为 对雌性啮齿动物的作用部分是通过其产物3-羟基-5-孕酮-20-酮 (3？，5？-THP)。在腹侧被盖区(VTA)，3？，5？-THP有促进 通过GABAA/苯二氮卓类(GBRs)和/或NMDA型的社会性行为 谷氨酸(NMDARs)，而不是通过细胞内孕激素受体。3？、5？-THP水平 中脑VTA既促进了社会性行为，也得到了加强。这个 孕烷X受体(PXR)介导多种受体的产生和/或代谢 神经生物学因素。PXR定位于大鼠中脑VTA。我们的假设是 依赖PXR的VTA中3？，5？-THP的生物合成是促进和/或 对社会性行为的反应。利用经典的行为内分泌学， 药理学和放射免疫分析方法，结合分子生物学工具 生物学，在社会性行为的老鼠模型中，目的将是调查。1)原因 PXR在中脑VTA的3？，5？-THP的活动，以促进社会性行为。2) 社会性行为对依赖PXR的中脑3，5-THP水平的影响如果 PXR和3？，5？-THP被改变以响应社会性行为，并阻止PXR 减弱行为诱导的3？，5？-THP，然后3？，5？-THP在中脑对 社会-性刺激是依赖于PXR的，并被其动态改变。3)3、5- THP可通过卵巢或卵巢外周产生的P的代谢在VTA中形成 肾上腺或中枢通过大脑中的生物合成。3？，5？-THP的PXR在VTA中的作用 从外周P的中枢生物合成和/或代谢中产生，以便于，或 将增加对社会性行为的调查。4)3？，5？-THP可能有PXR- 涉及GBR和/或NMDAR的依赖行动。3？5？的行为影响 THP，或3？，5？-THP的形成是对社会性行为的回应，部分原因是 将审查GBR和/或NMDAR的PXR依赖效应。侦察小说 3？，5？-THP的行为功能将扩展我们对神经生物学的认识 促孕素，与社会性行为相关，以及它们与 调节情绪。3？，5？-THP参与应激调节、病理生理学和/或 神经精神障碍的治疗。因此，对3？、5？THP的作用有了进一步的认识 和机制，以加强生殖/社会纽带，最大限度地减少攻击性，影响 社会行为的情感方面，以及调节对压力的反应，都是必不可少的。

Progesterone (P) mediates exploration, anxiety, social and sexual (socio-sexual) behaviors of female rodents in part through actions of its product, 3¿-hydroxy-5¿-pregnan-20-one (3¿,5¿-THP). In the ventral tegmental area (VTA), 3¿,5¿-THP has actions to facilitate socio-sexual behavior through GABAA/Benzodiazepine (GBRs) and/or NMDA type glutamate (NMDARs), rather than via intracellular progestin receptors. 3¿,5¿-THP levels in the midbrain VTA both facilitate, and are enhanced by, socio-sexual behavior. The pregnane X receptor (PXR) mediates the production of, and/or metabolism to, various neurobiological factors. PXR is localized to the midbrain VTA of rats. Our hypothesis is that PXR-dependent biosynthesis of 3¿,5¿-THP in the VTA underlies facilitation of, and/or response to, socio-sexual behaviors. Using classic behavioral endocrinology, pharmacology, and radioimmunoassay methods, in conjunction with tools of molecular biology, in a rat model of socio-sexual behaviors, aims will be to investigate. 1) The causal actions of PXR in the midbrain VTA for 3¿,5¿-THP to facilitate socio-sexual behaviors. 2) The effects of socio-sexual behaviors on PXR-dependent midbrain 3¿,5¿-THP levels. If PXR and 3¿,5¿-THP are altered in response to socio-sexual behaviors, and blocking PXR attenuates behavior-induced 3¿,5¿-THP, then effects of 3¿,5¿-THP in the midbrain to mediate, and be dynamically altered by, socio-sexual stimuli are PXR-dependent. 3) 3¿,5¿- THP can be formed in the VTA from metabolism of P produced peripherally by ovaries or adrenals or centrally via biosynthesis in brain. The role of PXR for 3¿,5¿-THP in the VTA to be produced from central biosynthesis and/or metabolism from peripheral P to facilitate, or be increased by, socio-sexual behaviors will be investigated. 4) 3¿,5¿-THP may have PXR- dependent actions involving GBRs and/or NMDARs. Whether behavioral effects of 3¿,5¿- THP, or 3¿,5¿-THP formation in response to socio-sexual behaviors, are in part due to PXR-dependent effects at GBRs and/or NMDARs, will be examined. Investigating novel behavioral functions of 3¿,5¿-THP will extend our knowledge of the neurobiology of progestogens, relevant for socio-sexual behaviors, and their connections to systems that regulate emotions. 3¿,5¿-THP is implicated in stress regulation, pathophysiology and/or treatment of neuropsychiatric disorders. Thus, further understanding of 3¿,5¿-THP's role and mechanisms to enhance reproduction/social bonds, minimize aggression, influence affective aspects of social behaviors, and to mediate responses to stress, are essential.