Animal models of alcoholism: genetic strategies and neurochemical mechanisms.

Evidence from human studies indicates that response to alcohol consumption and the probability of developing alcoholism have a heritable basis. The involvement of several genes encourages the application of classical genetics to elucidate the genetic basis of alcohol abuse. Quantitative genetics can provide evidence for modes of inheritance and estimates of gene number. Therefore, inbred strains and selective breeding programmes have been used to demonstrate a genetic basis for the physiological and behavioural effects of ethanol in rodents. Neurochemical studies have shown that ethanol has effects on membrane fluidity, and on membrane receptors, ion channels and enzymes (Fig. 1). Comparison of these in animal lines selected for a particular response (or lack of response) to ethanol has disclosed differences in membrane composition (notably in polysialogangliosides), and in the functioning of NaK-ATPase, Na+ channels and gamma-aminobutyric acid (GABAA) receptors. Not all of these effects were observed at relevant ethanol concentrations, but differences in the properties of GABAA receptors between lines are the most compelling. Thus classical genetic strategies, while labour intensive with respect to the generation and maintenance of animal lines, have proven useful in dissecting the molecular, cellular and behavioural effects of alcohol and their genetic variability.