Measuring the Aversive Effects of Alcohol Withdrawal

描述（由申请人提供）：有人假设，酒精戒断的厌恶性动机效应可能导致饮酒;然而，尚不清楚这些厌恶性效应是增加还是减少饮酒。这个R 03小额赠款提案的广泛，长期目标是开发一种敏感和可靠的位置条件反射技术来测量酒精戒断对小鼠的不良动机影响。具体目标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反射位置厌恶。这一目标将通过操纵调节会话持续时间、酒精戒断期间的调节时间、调节试验次数和酒精剂量来实现。具体目标2的目标是研究有助于酒精戒断的厌恶效应的潜在机制，并操纵酒精戒断的条件性位置厌恶的强度。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）对酒精戒断条件性位置厌恶程度的影响来实现。一个新的地方条件反射技术的发展，以衡量酒精戒断小鼠的厌恶效应将提供基本的方法，用于随后的R 01应用程序，将检查酒精戒断和饮酒行为的遗传小鼠模型中的厌恶动机效应的敏感性之间的遗传和神经生物学的关系。这种地方条件反射技术将是一个有价值的工具，酒精研究界研究的潜在机制，有助于不同的敏感性，酒精戒断的厌恶性影响。使用这种位置条件反射技术的研究可能会提供重要的信息，这将导致开发新的行为和药物治疗酒精中毒。

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.