Chronobiology of alcohol: animal models

酒精的时间生物学：动物模型

• 批准号: 6731431
• 负责人: ALAN M ROSENWASSER
• 金额: $ 13.24万
• 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/6731431
• 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）： 一些汇聚的证据表明，酒精摄入量与人类和实验动物的昼夜节律有关。因此，在人类和实验动物中，自愿饮酒和酒精敏感性是由一天中的时间（昼夜节律阶段）调节的，而饮酒和戒酒会改变睡眠和昼夜节律。事实上，酒精引起的睡眠和昼夜节律改变很可能会导致过度饮酒和酗酒对健康造成负面影响。然而，迄今为止，酒精时间生物学研究的一个主要缺点是未能确定酒精引起的睡眠和昼夜节律破坏是否是由酒精对潜在昼夜节律起搏器的药理作用介导的。此外，之前关于酒精时间生物学的动物研究未能利用经过充分验证的人类酗酒动物模型。本提案中提出的研究旨在明确解决现有文献中的这些缺点。具体来说，这些研究将（1）在饮酒之前，检查选择性饲养的酒精偏好和不偏好酒精的大鼠中基于遗传的酒精偏好和昼夜节律之间的关系，（2）表征过量饮酒的时间生物学影响- 像饮酒一样，让嗜酒的老鼠反复饮酒和戒酒，从而模拟人类酗酒者反复复发的影响，（3）探索急性和慢性酒精治疗对酒精治疗影响的能力叙利亚仓鼠的昼夜节律起搏器因其高度精确的活动节律而成为时间生物学研究中的重要动物模型，并且（4）确定了特定酒精敏感神经递质受体（GABA-A 受体）在介导药物药理作用中的可能作用酒精对昼夜节律起搏器的影响。这些研究的结果将极大地有助于了解人类酗酒者睡眠和昼夜节律紊乱的原因和后果。