Measuring the Aversive Effects of Alcohol Withdrawal

描述(由申请人提供)：已经假设戒酒的厌恶动机效应会导致饮酒；然而，尚不清楚这些厌恶效应是增加还是减少饮酒。这项R03小额赠款提案的广泛和长期目标是开发一种灵敏和可靠的场所条件反射技术来测量小鼠戒酒的厌恶动机效应。具体目标1的目标是确定将在小鼠中产生对酒精戒断的条件性位置厌恶的条件性参数。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的目的是调查导致戒酒厌恶效应的潜在机制，并操纵对戒酒的条件性场所厌恶的强度。这一目标将通过检测行为操作(惊厥诱导)和药物操作(GABAA受体拮抗剂)对酒精戒断的条件性位置厌恶程度的影响来实现。开发一种新的场所条件反射技术来测量小鼠戒酒的厌恶效应，这将为随后的R01应用程序提供基本的方法学，该应用程序将在酒精中毒的遗传小鼠模型中检查对酒精戒断的厌恶动机效应的敏感性和酒精饮酒行为之间的遗传和神经生物学关系。对于酒精研究界来说，这种位置条件反射技术将是一个有价值的工具，可以用来研究导致对酒精戒断的厌恶效应敏感性差异的潜在机制。使用这种场所条件反射技术的研究可能会提供重要的信息，这些信息将导致开发治疗酒精中毒的新的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.