ALCOHOL, GABA AND HORMONES: PHYSIOLOGY OF SUBUNIT CHANGE

描述：(改编自《调查者摘要》)众所周知 经前综合症(PMS)与酒精摄入量增加有关， 然后可能会起到抵消经前焦虑症的作用。这样做的目的是 本研究旨在探讨酒精对P期GABA功能的调节作用 戒断，一种经前综合症的啮齿动物模型，作为一种可能的机制，可以解释 月经前饮酒量增加。此外, 这一范例将允许我们评估酒精在GABA条件下的影响 生理相关激素产生的受体亚单位可塑性 改变。在这个模型中，动物在体内暴露于黄体酮三次 治疗结束后24小时进行检测。之前的研究结果来自 本实验提示，从GABA调节的3aOH-5apregnan-20-one中撤除 使用这一范例会导致焦虑和癫痫易感性增加 导致总积分GABA门控电流的降低 海马锥体细胞较快的衰变时间常数。GABA的这种变化 目前的动力学是由于GABA的A4亚单位显著增加 受体。本研究的目的是确定A4的效果 乙醇亚基上调对GABA门控电流的影响及其抑制作用 从海马片制备中记录的突触电流(mIPSCs和 SIPSCs)与A4亚单位水平相关。这 研究将测试两种可能起到缓解作用的潜在机制 经前综合征症状使用急性和持续的酒精治疗。这是我们的假设 急性乙醇将增加峰值GABA门控电流，同时持续 服用乙醇会降低A4亚单位的水平 随着GABA门控电流衰减时间在P之后恢复到控制水平 戒烟。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，这是一种缓解焦虑的时尚。了解 与酒精效应中激素相关变化有关的生理变化 可能会对导致酒精的潜在机制提供更多的见解 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.