Alcohol Reinforcement and Voluntary Ethanol Consumption Ting-Kai Li, Rainer Spanagel, Giancarlo Colombo, William J. McBride, Linda J. Porrino, Tsutomu Suzuki, and Zachary A. Rodd-Henricks This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The organizer/chair was Ting-Kai Li and the co-chair was Rainer Spanagel. The presentations were (1) Genetic differences in alcohol drinking and reinforcement: The sP and sNP Rats, by Giancarlo Co- lombo; (2) Ventral tegmental area—Neuroanatomical substrate for alcohol reinforcement, by William J. McBride; (3) Metabolic mapping of alcohol reinforcement, by Linda J. Porrino; (4) Role of opioid recep- tors in the ethanol-induced place preference in rats exposed to conditioned fear stress, by Tsutomu Suzuki; and (5) Repeated deprivations enhance the reinforcing properties of ethanol in alcohol preferring (P) rats, by Zachary A. Rodd-Henricks. Key Words: Alcohol, Genetics, Ventral Tegmental Area, Opioid Receptors, Rat. I T IS ACCEPTED widely that both genetic and environ- mental factors contribute to the risk for alcohol abuse and alcoholism. Research in population-based samples also has identified genetic and environmental components of variance in alcohol drinking behavior itself in the general population. Whereas shared environmental influences largely determine the onset of drinking, addictive genetic influences become increasingly important in explaining quantity and frequency of drinking in those who have ini- tiated drinking (Viken et al., 1999). A significant research challenge is, therefore, elucidation of the nature of biolog- ical variation in alcohol-seeking behavior and the influence of environmental factors and drinking history on this be- havior. For example, is alcohol inherently more reinforcing in some individuals than others? Does tolerance develop more rapidly and to a greater degree in some individuals than others? Are some individuals more susceptible to alcohol dependence and withdrawal than others? How do these phenotypes relate? What are the neurobiological bases of these responses to ethanol? Because of the ex- pense and inherent limitations of this kind of research in humans (and nonhuman primates), most of our knowledge comes from studies in rodent experimental animal models. This symposium presented recent research findings that explored the genetic and neurobiological underpinnings of alcohol drinking behavior and alcohol reinforcement in selectively bred and common stock rat models. Rats and mice, in the aggregate, do not like to drink aqueous solutions of ethanol in concentrations greater than 5% and do not attain blood alcohol concentrations per- ceived to be “intoxicating.” The question had been raised in the past whether it is possible to develop a laboratory-based animal model to study alcoholism (abnormal alcohol- seeking behavior) and the effects of neuroadaptive re- sponses to alcohol on drinking behavior (Cicero, 1979). However, there is large within-species variation in alcohol preference (Richter and Campbell, 1940) and, beginning in the 1950s, investigators from Chile, Finland, the United States, and Canada successfully developed, through selec- tive breeding, lines of rats that voluntarily would consume large amounts of alcohol. This genetic approach led to rat and mouse models for the study of alcoholism-related en- dophenotypes, namely, alcohol preference (alcohol seek- ing), acute sensitivity to alcohol (inherent neurosensitivity and within-session tolerance), and alcohol-withdrawal re- actions (Browman et al., 2000; Crabbe and Li, 1995). Among the pairs of rodent lines that were selected for high/low alcohol preference and consumption are the Uni- versity of Chile B and A rats, Alko alcohol (AA) and Alko nonalcohol (ANA) rats, alcohol-preferring (P) and alcohol- nonpreferring (NP) rats, high–alcohol-drinking (HAD) and low–alcohol-drinking (LAD) rats, Sardinian alcohol- preferring (sP) and -nonpreferring (sNP) rats, and the From Indiana University School of Medicine (T-KL, WJM, ZAR-H), Indianapolis, Indiana; Central Institute of Mental Health (RS), University of Heidelberg, Mannheim, Germany; University of Cagliari (GC), Cagliari, Italy; Wake Forest University School of Medicine (LJP), Winston-Salem, North Carolina; and Hoshi University (TS), Tokyo, Japan. Received for publication January 11, 2001; accepted January 11, 2001. Supported by a travel grant from the Alcoholic Beverage Medical Research Foundation and by Grants P50 AA07611 (T-KL), P50 AA07611 and R01 AA12262 (WJM), R01 AA09291 (LJP), and P50 AA07611, R01 AA11261, and T32 AA07462 (ZR-H) from NIAAA; by Neuroscienze S.c.a.r.l., Cagliari, Italy (GC); and by the Ministry of Health and Welfare, the Ministry of Education, Science, Sports and Culture of Japan (TS). Reprint requests: Ting-Kai Li, MD, Department of Medicine, Indiana University School of Medicine, 545 Barnhill Drive, Emerson 421, Indianap- olis, IN 46202; Fax: 317-274-4311; E-mail: tkli@iupui.edu Copyright © 2001 by the Research Society on Alcoholism. 0145-6008/01/2505-0117$03.00/0 ALCOHOLISM:CLINICAL AND EXPERIMENTAL RESEARCH Vol. 25, No. 5 May Supplement 2001 Alcohol Clin Exp Res, Vol 25, No 5, 2001: pp 117S–126S 117S