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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AA013893-02
Application #
6850912
Study Section
Health Services Research Review Subcommittee (AA)
Program Officer
Grandison, Lindsey
Project Start
2004-02-06
Project End
2007-01-31
Budget Start
2005-02-01
Budget End
2006-01-31
Support Year
2
Fiscal Year
2005
Total Cost
$134,182
Indirect Cost
Name
University of Maine Orono
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
186875787
City
Orono
State
ME
Country
United States
Zip Code
04469
Rosenwasser, Alan M; McCulley 3rd, Walter D; Fecteau, Matthew (2014) Circadian activity rhythms and voluntary ethanol intake in male and female ethanol-preferring rats: effects of long-term ethanol access. Alcohol 48:647-55
Logan, Ryan W; Seggio, Joseph A; Robinson, Stacy L et al. (2010) Circadian wheel-running activity during withdrawal from chronic intermittent ethanol exposure in mice. Alcohol 44:239-44
Rosenwasser, Alan M; Clark, James W; Fixaris, Michael C et al. (2010) Effects of repeated light-dark phase shifts on voluntary ethanol and water intake in male and female Fischer and Lewis rats. Alcohol 44:229-37
Seggio, Joseph A; Logan, Ryan W; Rosenwasser, Alan M (2007) Chronic ethanol intake modulates photic and non-photic circadian phase responses in the Syrian hamster. Pharmacol Biochem Behav 87:297-305
Clark, James W; Fixaris, Michael C; Belanger, Gabriel V et al. (2007) Repeated light-dark phase shifts modulate voluntary ethanol intake in male and female high alcohol-drinking (HAD1) rats. Alcohol Clin Exp Res 31:1699-706
Spanagel, Rainer; Rosenwasser, Alan M; Schumann, Gunter et al. (2005) Alcohol consumption and the body's biological clock. Alcohol Clin Exp Res 29:1550-7
Rosenwasser, Alan M; Fecteau, Matthew E; Logan, Ryan W et al. (2005) Circadian activity rhythms in selectively bred ethanol-preferring and nonpreferring rats. Alcohol 36:69-81