Progestins' non-genomic actions for socio-sexual behavior

预后（P）介导探索，焦虑，社会和性（社会性）行为 雌性啮齿动物的部分作用是通过其产品，3 <$-羟基-5 <$-葡聚糖-20-酮 （3 <$，5 <$-THP）。在腹侧被盖区（VTA），3 <$，5 <$-THP具有促进 通过GABAA/苯二氮卓类（GBR）和/或NMDA类型的社会性行为 谷氨酸（NMDAR），而不是通过细胞内的谷氨酸受体。3 <$，5 <$-THP水平 中脑腹侧被盖区既能促进社会性行为，也能被社会性行为增强。的 胆固醇X受体（PXR）介导各种代谢产物的产生和/或代谢， 神经生物学因素PXR定位于大鼠的中脑VTA。我们的假设是 腹侧被盖区3 <$，5 <$-THP的PXR依赖性生物合成是促进和/或 对社会性行为的反应使用经典的行为内分泌学， 药理学和放射免疫测定方法，结合分子生物学工具， 生物学，在一个社会性行为的大鼠模型，目的将是调查。1)的因果 PXR在中脑腹侧被盖区对3 <$，5 <$-THP的作用促进社会性行为。（二） 社会性行为对PXR依赖的中脑3 <$，5 <$-THP水平的影响如果 PXR和3 <$，5 <$-THP在对社会性行为的反应中发生改变， 减弱行为诱导的3-THP，然后3-THP在中脑的作用， 介导，并动态地改变，社会性刺激是PXR依赖的。3)3、5、- THP可以在腹侧被盖区由卵巢外周产生的P代谢形成， 肾上腺或中枢通过脑中的生物合成。PXR对3 <$，5 <$-THP在VTA中的作用 由外周P的中枢生物合成和/或代谢产生，以促进，或 增加，将调查社会性行为。4)3 <$，5 <$-THP可能有PXR- 涉及GBR和/或NMDAR的相关行动。3 <$，5 <$的行为效应是否- THP或3 <$，5 <$-THP的形成是对社会性行为的反应，部分原因是 将检查GBR和/或NMDAR的PXR依赖性效应。调查小说 3 <$，5 <$-THP的行为功能将扩展我们对神经生物学的知识， 孕激素，与社会性行为有关，以及它们与系统的联系， 调节情绪3 <$，5 <$-THP参与应激调节、病理生理学和/或 神经精神疾病的治疗。因此，进一步了解3 <$，5 <$-THP的作用 和机制，以加强生殖/社会纽带，尽量减少侵略，影响 社会行为的情感方面，并调解对压力的反应，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.