Recent Animal Models of Alcoholism

Alcohol Research & Health,  Spring, 2000  by Rainer Spanagel

• E-mail
• Print
• Link

Animal models on alcohol preference have a long-standing tradition in biomedical research on alcoholism. However, these models allow only limited conclusions regarding alcohol addiction. Therefore, during the past 15 years, researchers have developed new animal models that mimic different aspects of human alcohol addiction, such as craving, relapse, and loss of control over drinking. These models include the reinstatement model, the alcohol deprivation model, and the point-of-no-return model. Some of these models have been pharmacologically validated with anticraving compounds that are used clinically for treating alcoholics. The detailed behavioral characterization of these new models and their pharmacological validation also allow researchers to study the neurochemical and molecular bases of addictive behavior. KEY WORDS: animal model; trend; research; AOD (alcohol or other drug) preference; AODD (AOD use disorder); relapse; AOD craving; AOD abstinence; anti-alcohol-craving agents; A AOD-seeking behavior

Researchers have known since 1940 that some rodents voluntarily consume alcohol in a laboratory setting. [1] One can also assume that voluntary alcohol consumption by rodents and other mammals occurs in the wild, because some mammals, including rodents, occasionally consume large amounts of rotten fruits and exhibit abnormal behavioral patterns that may result from intoxication. Consequently, voluntary alcohol consumption, which is often observed in combination with palatable food or fluid intake, can be considered a part of the normal behavioral repertoire of rodents. These observations position rats and mice as ideal subjects for studying various aspects of human alcohol use, including alcohol reinforcement. [2]

One commonly used approach to modeling human alcohol consumption in rodents are alcohol preference studies, in which the animals are given a choice between water and alcohol solutions and the investigators measure the amount consumed of each fluid. In comparison to other behavioral studies (e.g., anxiety tests), data on alcohol consumption levels obtained by such alcohol preference experiments show little variation, even when conducted in different laboratories (Crabbe et al. 1999) and different settings. Moreover, because alcohol reinforcement is mediated by brain structures that have been strongly conserved during evolution (i.e., subcortical structures), rodent studies have an enormous potential for further elucidating the neurobiological basis of alcohol consumption and alcohol reinforcement processes in humans.

This article presents several rodent models that have been used in recent years to study various aspects of alcohol addiction. The article first reviews traditional alcohol preference models and their limitations. It then describes newer models aimed at helping researchers investigate the rodent equivalent of complex human behaviors, such as craving, relapse, and loss of control over drinking. These models have been validated in pharmacological studies and have provided some insight into the neurochemical and cellular changes underlying addictive behaviors.

ALCOHOL PREFERENCE MODELS

As mentioned previously, researchers have conducted numerous alcohol preference studies in which the animals were offered a free choice between water and alcohol solutions of various concentrations. These studies found that when offered low alcohol concentrations (i.e., up to 6 percent weight/volume), which have a "sweet" taste, rats and mice generally drink more alcohol than water. At higher alcohol concentrations, however, at which the taste of the solution usually is aversive to rodents, large differences exist among individuals and among strains in alcohol preference. These observations suggest that animals primarily prefer alcohol because of such factors as taste, rather than because of its stimulatory effect on the central nervous system. Only a few animals exhibit an alcohol preference that results from alcohol's pharmacological (e.g., reinforcing) effects.

The large variability in alcohol preference among individual animals and strains has allowed researchers to selectively breed rats for differential alcohol preference, generating pairs of animal strains that are characterized by particularly low or high alcohol consumption levels. The best studied pairs of lines were generated in Finland, the United States, and Sardinia. The Finnish model--called Alko Alcohol (AA) and Alko Nonalcohol (ANA) rats--comprises two strains of albino rats that based on their selection or rejection of a 10-percent alcohol solution and water, were selectively bred starting in 1963 (Eriksson 1968). The alcohol-preferring (P) rats, originally bred in Indiana, voluntarily consume 5-8 grams of alcohol per kilogram of body weight per day (g/kg/day), attaining blood alcohol concentrations of 50-200 mg/100 mL, whereas the non-alcohol-preferring rats (NP) consume less than 0.5 g/kg/day alcohol (McBride and Li 1998). The Sardinian alcohol-preferring (sP) rats also have been selectively bred f or high alcohol preference and consumption for more than 20 years (Colombo 1997). These models have been used as a tool for characterizing the behavioral, neurochemical, and molecular correlates of differential voluntary alcohol consumption and preference.