What aspects of human alcohol use disorders can be modeled using selectively bred rat lines?
The use of selective breeding to produce animal models for the study of alcohol abuse and alcoholism represents one of the major advances in the field of alcohol research. Rats selectively bred for alcohol preference and alcohol nonpreference have been useful to both preclinical and clinical investigators in the alcohol research community for studying the behavioral, neurobiological, and molecular basis of alcohol drinking, for identifying the genes that may contribute to the development of alcohol abuse and alcoholism, and for evaluating the utility of drugs aimed at reducing alcohol intake and preventing alcohol relapse. Rats selectively bred for alcohol preference (alcohol preferring or "P" line) have enhanced responsiveness to the low dose reinforcing effects of alcohol, less aversion to moderate/high doses of alcohol, and are able to develop tolerance to the aversive effects of alcohol more rapidly and to maintain tolerance longer than rats selectively bred for alcohol nonpreference (alcohol nonpreferring or "NP" line). The increased potency of low-dose alcohol as a reinforcer for P rats might be expected to foster and maintain alcohol drinking. Weaker aversion to the pharmacological effects of moderate/high doses of alcohol in the P line would allow P rats to drink more alcohol than NP rats before the postingestional effects become aversive. Rapid induction of tolerance to the aversive effects of alcohol with repeated bouts of voluntary alcohol drinking, as well as persistence of alcohol tolerance in rats of the P line might serve to maintain alcohol drinking. These are powerful mechanisms that may serve to promote and maintain a high alcohol drinking behavior. Although these rat lines have been used to address several characteristics of excessive alcohol consumption in humans, they have not yet been used to model several aspects of human alcohol use disorders. New applications of these selectively bred rat lines are discussed which may further our understanding of the factors contributing to alcohol abuse and alcoholism.
Froehlich
J C
JC
Chancellor's Professor and Professor of Medicine, Cellular and Integrative Physiology and Medical Neurobiology, Indiana University School of Medicine, Indiana University-Purdue University Indianapolis, IN 46202, USA. jcfroehl@iupui.edu
D000437:Alcoholism / Q000209:etiology; D000818:Animals; D006801:Humans; D023421:Models, Animal; D051381:Rats; D011919:Rats, Inbred Strains; D057170:Translational Research, Biomedical