Chronobiology of alcohol: animal models

酒精的时间生物学：动物模型

• 批准号: 6850912
• 负责人: ALAN M ROSENWASSER
• 金额: $ 13.42万
• 依托单位: UNIVERSITY OF MAINE ORONO
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-02-06 至 2007-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6850912
• 关键词: GABA receptor; alcoholism /alcohol abuse; behavioral genetics; bioperiodicity; comorbidity; disease /disorder model; ethanol; hamsters; inhibitor /antagonist; laboratory rat; neuropharmacology; sleep disorders; triazolam

DESCRIPTION (provided by applicant): Several converging lines of evidence link alcohol intake to circadian biological rhythms in both humans and experimental animals. Thus, voluntary alcohol intake and alcohol sensitivity are modulated by time-of-day (circadian phase), while alcohol consumption and alcohol withdrawal alter sleep and circadian rhythms, in both humans and experimental animals. Indeed, it is likely that alcohol-induced alterations in sleep and circadian rhythmicity contribute to the negative health consequences of excessive alcohol consumption and alcoholism. Nevertheless, a major shortcoming of chronobiological research on alcohol till now has been the failure to determine whether alcohol-induced disruptions of sleep and circadian rhythms are mediated by pharmacologic effects of alcohol on the underlying circadian pacemaker. In addition, previous animal research on the chronobiology of alcohol has failed to utilize well-validated animal models of human alcoholism. The studies presented in this proposal have been designed explicitly to address these shortcomings in the existing literature. Specifically, these studies will (1) examine relationships between genetically-based alcohol preference and circadian rhythms in selectively-bred alcohol preferring and alcohol-non-preferring rats, prior to experience with alcohol drinking, (2) characterize the chronobiological effects of excessive alcoholic-like drinking in alcohol-preferring rats subjected to repeated periods of alcohol access and alcohol withdrawal, thus simulating the effects of repeated relapse in human alcoholics, (3) explore the ability of both acute and chronic alcohol treatments to affect the circadian pacemaker in Syrian hamsters, an important animal model in chronobiological research due to its highly precise activity rhythm, and (4) identify the possible role of a specific alcohol-sensitive neurotransmitter receptor, the GABA-A receptor, in mediating the pharmacologic effects of alcohol on the circadian pacemaker. The results of these studies will contribute substantially to understanding both the causes and the consequences of sleep and circadian rhythm disruptions occurring in human alcoholics.

描述（由申请人提供）： 几种融合的证据线将酒精摄入量与人类和实验动物的昼夜节律生物节奏联系起来。因此，在人类和实验动物中，饮酒和饮酒会改变睡眠和昼夜节律。确实，酒精引起的睡眠和昼夜节律的改变可能导致过度饮酒和酒精中毒的负面影响。然而，到目前为止，对酒精的时间生物学研究的主要缺点是未能确定酒精引起的睡眠和昼夜节律是否是通过酒精对基础昼夜节律起搏器的药理作用介导的。此外，先前关于酒精年代生物学的动物研究未能利用人类酒精中毒的验证动物模型。该提案中提出的研究已明确设计，目的是解决现有文献中的这些缺陷。具体而言，这些研究将（1）研究基于遗传性的酒精偏好和昼夜节律在有选择性繁殖的酒精偏爱和饮酒 - 非偏爱大鼠中，在接受酒精饮酒之前，（2）表征过多的酒精性含量的时间。 - 像饮酒一样饮酒，受到重复的酒精入口和戒酒的重复时期，从而模拟了人类酒精中毒反复复发的影响，（3）探索急性和慢性酒精治疗的能力，影响叙利亚昼夜节律的起搏器仓鼠，由于其高度精确的活性节奏而在时间生物学研究中是一个重要的动物模型，（4）确定特定酒精敏感的神经递质受体（GABA-A受体）在介导酒精对昼夜节律的药理作用中的可能作用起搏器。这些研究的结果将有助于了解人类酒精中毒发生的睡眠和昼夜节律中断的原因和后果。