SEROTONERGIC CHARACTERIZATION OF ETHANOL WITHDRAWAL

该提案旨在扩大乙醇特性的实验 戒断症状及其机制。滥用 乙醇会产生依赖性，其特征是戒断模式 包括主观症状，如焦虑。虽然关键角色 这些症状在启动和维持乙醇滥用是很好的 公认的是，对主观症状的动物研究已经 难在本供资期间，情况表明， 乙醇戒断会产生类似PTZ的内部刺激， 以产生关于戒断的主观症状的参数数据。的 在乙醇戒断过程中发生的HZ样刺激受到 作用于γ-氨基丁酸-A型（GABAA）受体的药物- 氯离子通道复合物然而，PTZ-IDS对 5-羟色胺（5-HT）系统的调节。5 HT系统已被 与乙醇依赖有关，并在我们自己的 使用其他行为测量的实验。为了更好 表征5 HT在乙醇依赖性发展中的作用， 退出使用药物歧视的方法，新的实验是 建议采用5 HT激动剂，1（3-氯苯基）哌嗪，mCPP，作为 一种辨别刺激，以表征动物模型的特征， 戒断症状提出了以下几点建议：1）证明mCPP IDS 在动物中，通过药物调节，所述药物是致焦虑的或 人类抗焦虑药，2）证明和表征自发性 在乙醇戒断期间发生mCPP样刺激， 作为累积乙醇的函数的刺激强度 剂量，3）通过选定的5-HT受体改变戒断刺激 亚型激动剂和拮抗剂，以及4）比较和对比PTZ 和mCPP刺激，以确定在乙醇戒断过程中， 5-HT和GABA系统在产生 类似“焦虑”的行为使用这种方法将提供重要的新 数据，并扩展我们在其他动物模型中获得的结果， 焦虑这项研究意义重大，因为它提供了信息， 与乙醇滥用的病因学和治疗直接相关。

This proposal seeks to expand experiments on characterizing ethanol withdrawal with respect to its symptoms and their mechanisms. Abuse of ethanol produces dependence characterized by a pattern of withdrawal consisting of subjective symptoms such as anxiety. Although the key role of these symptoms in initiating and maintaining ethanol abuse is well recognized, animal research on the subjective symptoms has been difficult. In the current funding period, it was demonstrated that ethanol withdrawal produces a PTZ-like internal stimulus that can be used to produce parametric data on the subjective symptoms of withdrawal. The HZ-like stimulus occurring during ethanol withdrawal was modulated by drugs acting at the gamma-amino butyric acid-type A (GABAA) receptor- chloride ion channel complex. However, PTZ-IDS was insensitive to modulation of brain serotonin (5HT) systems. The 5HT systems have been implicated in ethanol dependence and found important in our own experiments employing other behavioral measures. In order to better characterize the role of 5HT in the development of ethanol dependence and withdrawal using drug discrimination approach, new experiments are proposed to employ a 5HT agonist, 1(3-chlorophenyl)piperazine, mCPP, as a discriminative stimulus to characterize an animal model of the withdrawal symptoms. It is proposed: 1) to demonstrate that the mCPP IDS in animals is modulated by drugs which are either anxiogenic or anxiolytic in humans, 2) to demonstrate and characterize the spontaneous occurrence of a mCPP-like stimulus during ethanol withdrawal in relation to the intensity of the stimulus as a function of cumulative ethanol dose, 3) to modify the withdrawal stimulus by selected 5HT receptor subtype agonists and antagonists, and 4) to compare and contrast the PTZ and mCPP stimuli during ethanol withdrawal to determine the manner in which the 5HT and GABA systems relate to one another in producing "anxiety"-like behavior. Use of this method will provide important new data and extend the results obtained in our other animal models of anxiety. This research is significant because it provides information directly related to etiology and treatment of ethanol abuse.