The Neurobiology of Alcoholism in Genetically Selected Rat Models

By Stewart, Robert B; Li, Ting-Kai | Alcohol Health & Research World, January 1, 1997 | Go to article overview

The Neurobiology of Alcoholism in Genetically Selected Rat Models


Stewart, Robert B, Li, Ting-Kai, Alcohol Health & Research World


Rats selectively bred for their tendency to drink large or small quantities of alcohol are a useful model for investigators examining the possible neurobiological processes underlying alcoholism. Studies with the alcohol-preferring (P) and alcoholnonpreferring (NP) and the high-alcohol-drinking (HAD) and low-alcohol-drinking (LAD) pairs of rat lines developed at Indiana University have illustrated differences in several behavioral and neurobiological characteristics associated with alcohol consumption. Specifically, compared with alcohol-avoiding rats, rats with an affinity for alcohol have a greater sensitivity to the stimulatory effects of low to moderate doses and a reduced sensitivity to the negative effects of high doses. Rats that voluntarily drink large quantities of alcohol also acquire tolerance to alcohol's aversive effects. In addition, these rats differ from their alcohol-avoiding counterparts in the levels of several chemical mediators (i.e., neurotransmitters) found in the brain, including serotonin, dopamine, gamma-aminobutyric acid (GABA), and the endogenous opioids. KEY WORDS: animal strains; selective breeding; AOD preference; amount of AOD use; AOD tolerance; neurotransmitters; reinforcement; drug therapy; literature review

Animal models have been critical to many areas of research, including the investigation of the behavioral Land neurobiological processes that may underlie alcohol abuse and alcoholism. The use of animals, rather than humans, in research has two advantages: (1) animal models allow a high degree of experimental control not possible with human subjects (i.e., scientists can focus solely on alcohol's effects without the interference of confounding factors that may accompany alcoholism in humans, such as liver damage, poor nutrition, or psychiatric disturbances) and (2) animal models permit the use of invasive procedures. This article describes the findings of studies on rats that have been specially bred for their tendencies to drink either large or small quantities of alcohol. In particular, the article focuses on characteristics associated with high and low levels of alcohol drinking that have been investigated in the specially bred lines of rats developed at Indiana University. TOLERANCE, DEPENDENCE, AND REINFORCEMENT

Historically, animal models of alcoholism have been used most extensively to study alcohol tolerance and physical dependence (see Kalant et al. 1971 for a seminal review in this field; see Kalant 1993 and Hoffman and Tabakoff 1996 for recent reviews on the mechanisms of tolerance and dependence). Tolerance to alcohol occurs when, following chronic consumption, higher doses of alcohol must be ingested to achieve a given effect. Consequently, researchers believe that tolerance accounts for increases in the amount of alcohol consumed over time. Physical dependence is indicated by signs of withdrawal resulting from the absence of alcohol in the body when drinking is discontinued. Because alcohol withdrawal symptomswhich range from anxiety, tremors, hypothermia, and sleep disturbances to hallucinations and seizures-are unpleasant (i.e., aversive), researchers hypothesize that physically dependent people drink to avoid or alleviate these symptoms. In fact, the development of tolerance and physical dependence are considered hallmarks of alcoholism.

These two processes, however, cannot account for the initiation of alcohol drinking or explain why relapse occurs in abstinent alcoholics long after the signs of physical dependence have disappeared. Thus, researchers continue to investigate additional behavioral and neurobiological factors that may underlie alcohol use. Recent studies have focused on a process called reinforcement. In behavioral psychology, reinforcement refers to the connection between a behavior and a stimulus whereby the chance of repeated behavior (e.g., alcohol-seeking) is enhanced if the behavior results in obtaining a reinforcing stimulus (e. …

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