What Aspects of Human Alcohol Use Disorders Can Be Modeled Using Selectively Bred Rat Lines?

Abstract

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.

Keywords :

• animal models
• translational research
• selectively bred rats

THE AUTHOR

Dr. Janice C. Froehlich received a B.S. from the University of California in 1971 and a Ph.D. from Syracuse University in 1978. She is a Chancellor's Professor of Medicine in the Division of Endocrinology and Metabolism with joint appointments as Professor in the Department of Cellular and Integrative Physiology and in Medical Neurobiology at the Indiana University School of Medicine. Dr. Froehlich's research program focuses on the hormonal, neurochemical, behavioral, and genetic factors that contribute to alcohol abuse and the development of alcoholism. She directs both preclinical and clinical studies on neuroendocrine and neurotransmitter systems that mediate many of the effects of alcohol such as euphoria, sedation, tolerance, and dependence. She also directs preclinical studies on the development of medications for the treatment of alcoholism. Dr. Froehlich is a Scientific Co-Director of the Indiana Alcohol Research Center, has served on the editorial board of national journals, as a member of study section of the National Institutes of Health, and as Vice Chancellor for Research at Indiana University-Purdue University Indianapolis. She has authored numerous papers, book chapters, and review articles and has supervised more than 50 graduate students and postdoctoral fellows.