ALCOHOL, GABA AND HORMONES: PHYSIOLOGY OF SUBUNIT CHANGE

描述：（改编自研究者摘要）众所周知， 经前综合征（PMS）与增加的乙醇消耗有关， 这可能会抵消经前焦虑。这样做的目的 本研究旨在检测P过程中乙醇对GABA功能调节的变化， 戒断，经前综合征的啮齿动物模型，作为一种可能的机制，可以解释 月经前饮酒量增加。此外，本发明还提供了一种方法， 这一范例将使我们能够评估乙醇在GABA条件下的作用， 生理相关激素产生的受体亚单位可塑性 变化对于该模型，将动物在体内暴露于孕酮三小时。 停止治疗后24小时进行检测。以前的调查结果来自 这个实验表明，从GABA调节的3aOH-5apregnan-20-one中撤出， 使用这种范例会导致焦虑和癫痫易感性增加， 总积分GABA门控电流的降低是由于 海马锥体细胞的衰减时间常数更快。GABA的这种变化 电流动力学是由于GABA α 4亚基的显著增加 受体的本研究的目的是确定a4 亚单位上调乙醇对GABA门控电流的影响和抑制作用 从海马切片制备物（mIPSC和 sIPSC）与α 4亚基水平相关。这 一项研究将测试两种可能的机制， 使用急性和持续乙醇治疗的PMS症状。我们假设 急性乙醇会增加GABA门控电流峰值， 给予乙醇将降低与此同时的A4亚单位的水平 P后GABA门控电流衰减时间恢复到对照水平 戒断乙醇对GABA功能的增强可能会增强 对患有经前综合症的人来说是一种抗焦虑的时尚。了解 与酒精效应相关的生理变化 可以提供更多的洞察潜在的机制，导致酒精 虐待

DESCRIPTION: (Adapted from the Investigator's Abstract) It is well known that pre-menstrual syndrome (PMS) is associated with increased ethanol consumption, which may then act to counteract premenstrual dysphoria. The purpose of this study is to examine changes in ethanol modulation of GABA function during P withdrawal, a rodent model of PMS, as a possible mechanism which may explain increased alcohol consumption during the pre-menstrual period. In addition, this paradigm will allow us to assess ethanol effects under conditions of GABA receptor subunit plasticity produced by physiologically relevant hormonal changes. For this model, animals are exposed in vivo to progesterone for three weeks and tested 24 hrs after cessation of treatment. Previous findings from this lab suggest that withdrawal from the GABA-modulatory 3aOH-5apregnan-20-one using this paradigm results in increased anxiety and seizure susceptibility due to decreases in total integrated GABA-gated current as a result of a markedly faster decay time constant for hippocampal pyramidal cells. This change in GABA current kinetics was due to significant increases in the a4 subunit of the GABA receptor. The goal of the present studies is to determine the effect of a4 subunit upregulation on ethanol effects on GABA-gated current and inhibitory synaptic currents recorded from the hippocampal slice preparation (mIPSCs and sIPSCs) correlated with a4 subunit levels using Western blot procedures. This study will test two potential mechanisms which may act to alleviate PMS-symptoms using acute and sustained ethanol treatment. It is our hypothesis that acute ethanol will increase peak GABA-gated current, while sustained ethanol administration will decrease levels of the a4 subunit in conjunction with return of GABA-gated current decay time to control levels following P withdrawal. Enhancement of GABA function by ethanol may then be reinforcing in an anxiolytic fashion to individuals suffering from PMS. Understanding the physiological changes involved in hormone-associated changes in alcohol effects may provide additional insight into potential mechanisms leading to alcohol abuse.