Introduction
Human studies are necessary to identify and classify the brain systems predisposing individuals to develop alcohol use disorders and those modified by alcohol, while animal models of alcoholism are essential for a mechanistic understanding of how chronic voluntary alcohol consumption becomes compulsive, how brain systems become damaged, and how damage resolves. Our current knowledge of the neuroscience of alcohol dependence has evolved from the interchange of information gathered from both human alcoholics and animal models of alcoholism. Together, studies in humans and animal models have provided support for the involvement of specific brain structures over the course of alcohol addiction, including the prefrontal cortex, basal ganglia, cerebellum, amygdala, hippocampus, and the hypothalamic–pituitary–adrenal axis. KEY WORDS: Alcohol dependence; alcoholism; chronic alcohol exposure; alcohol and other drug effects and consequences; genetic factors; environmental factors; brain; neurobiology; translational studies; human studies; animal studies; animal models
What currently is known about alcohol’s effects on the brain has benefited from translational research—the parallel study of humans with alcohol dependence and of animal models that mimic targeted aspects of this complex disease. Human studies provide a full depiction of the consequences of chronic alcohol exposure, but they are limited by ethical considerations for experimentation of rigorous controls of relevant variables. Animal models, on the other hand, can distinguish components of the addiction processes but cannot fully represent the human condition.
In humans, 40 to 60 percent of the risk for alcoholism can be attributed to genetic factors. These genetic factors interact with environmental factors (e.g., early-life stress, family structure, peer pressure, or the social environment; McKenzie et al. 2005) to influence an individual’s vulnerability to alcohol problems (Prescott and Kendler 1999). The genetic component has been modeled by breeding animal strains (predominantly rats and mice) with a high preference for alcohol (e.g., the alcohol preferring [P] and nonpreferring [NP] rats, high-alcohol– drinking [HAD] and low-alcohol– drinking [LAD] rats, the high-alcohol– preferring [HAP] mouse, and C57 black mice). The environment also has been modeled, for example, by separating young monkeys from their mothers, which reproduces early-life stress
