Measuring the Aversive Effects of Alcohol Withdrawal

描述（由申请人提供）：假设酒精戒断的厌恶动机效应可以促进饮酒；然而，尚不清楚这些不良影响是增加还是减少饮酒。这项R03小额拨款提案的广泛、长期目标是开发一种敏感、可靠的场所条件反射技术，以测量小鼠酒精戒断的厌恶动机效应。特异性目标1的目标是确定条件反射参数，这些参数将在小鼠中产生对酒精戒断的条件厌恶。这一目标将通过控制条件反射持续时间、戒酒期间的条件反射时间、条件反射试验次数和酒精剂量来实现。具体目标2的目标是研究导致酒精戒断的厌恶效应的潜在机制，并操纵对酒精戒断的条件场所厌恶的强度。这一目标将通过检查行为操作（惊厥诱导）和药理学操作（GABAA受体拮抗剂）对酒精戒断的条件性场所厌恶程度的影响来实现。一种测量小鼠酒精戒断的厌恶效应的新场所条件反射技术的发展将为随后的R01应用提供基本方法，该应用将检查酒精戒断的厌恶动机效应敏感性和酒精饮酒行为在酒精遗传小鼠模型中的遗传和神经生物学关系。这种场所调节技术将成为酒精研究界研究导致对酒精戒断不良反应敏感性差异的潜在机制的宝贵工具。使用这种位置调节技术的研究可能会提供重要的信息，这将导致开发新的酒精中毒行为和药物治疗方法。

DESCRIPTION (provided by applicant): It has been hypothesized that the aversive motivational effects of alcohol withdrawal can contribute to alcohol drinking; however, it is not clear whether these aversive effects increase or decrease drinking. The broad, long-term objective of this R03 Small Grant proposal is to develop a sensitive and reliable place conditioning technique to measure the aversive motivational effects of alcohol withdrawal in mice. The goal of Specific Aim 1 is to identify conditioning parameters that will produce a conditioned place aversion to alcohol withdrawal in mice. This goal will be achieved by manipulating conditioning session duration, tine of conditioning during alcohol withdrawal, number of conditioning trials, and alcohol dose. The goal of Specific Aim 2 is to investigate the underlying mechanisms that contribute to the aversive effects of alcohol withdrawal and to manipulate the strength of conditioned place aversion to alcohol withdrawal. This goal will be achieved by examining the effect of a behavioral manipulation (convulsion induction) and a pharmacological manipulation (GABAA receptor antagonism) on the magnitude of conditioned place aversion to alcohol withdrawal. The development of a new place conditioning technique to measure aversive effects of alcohol withdrawal in mice will provide the basic methodology to be used in a subsequent R01 application that will examine genetic and neurobiological relationships between sensitivity to aversive motivational effects of alcohol withdrawal and alcohol drinking behavior in a genetic mouse model of alcoholism. This place conditioning technique will be a valuable tool for the alcohol research community to study the underlying mechanisms that contribute to differences in sensitivity to the aversive effects of alcohol withdrawal. Studies using this place conditioning technique are likely to provide important information that will lead to the development of novel behavioral and pharmacological treatments for alcoholism.