Measuring the Aversive Effects of Alcohol Withdrawal

测量酒精戒断的不良影响

• 批准号: 7094224
• 负责人: JULIA ANN CHESTER
• 金额: $ 4.88万
• 依托单位: PURDUE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-15 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7094224
• 关键词: GABA receptor; alcoholic beverage consumption; avoidance behavior; behavior modification; behavior test; behavioral /social science research tag; drug /alcohol abstinence; drug withdrawal; laboratory mouse; motivation; negative reinforcements; neurotransmitter antagonist; operant conditionings; receptor expression; statistics /biometry; substance abuse related behavior

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.

描述（由申请人提供）：假设戒酒的厌恶动机作用会导致饮酒；但是，尚不清楚这些厌恶作用是增加还是减少饮酒。该R03小型赠款提案的广泛长期目标是开发一种敏感且可靠的地方调节技术，以衡量小鼠酒精戒断的厌恶动机作用。特定目标1的目的是确定可以在小鼠中产生条件地位戒酒的条件参数。该目标将通过操纵调节持续时间，戒酒期间的调理，调节次数和酒精剂量来实现。特定目的2的目的是研究有助于戒酒的厌恶作用并操纵条件的场所厌食强度对戒酒的强度的基本机制。该目标将通过检查行为操纵（抽搐诱导）和药理学操纵（GABAA受体拮抗作用）的影响来实现此目标。新地点调节技术的开发以测量小鼠饮酒的厌恶作用，将为随后的R01应用提供基本方法，该方法将在随后的R01应用中使用，该方法将研究对酒精饮酒行为的厌恶动机敏感性在遗传小鼠模型中的厌恶动机和酒精饮酒行为的厌恶动机之间的敏感性。对于酒精研究界，该地点调节技术将是研究基本机制的宝贵工具，这些机制导致对戒酒的厌恶效果的敏感性差异。使用该地点调节技术的研究可能会提供重要信息，从而导致酗酒的新型行为和药理学治疗。