Pharmacogenetic models of alcoholism.

This article reviews recent efforts in developing laboratory animal models for the study of alcoholism and abnormal alcohol-seeking behavior. Through selective breeding, stable lines of rats that reliably exhibit high and low voluntary alcohol consumption have been raised. The high preference animals self-administer ethanol by free-choice drinking, and operantly for intragastric infusion, in amounts that produce intoxication. With chronic free-choice drinking, the preferring rats develop tolerance and physical dependence. Low to moderate concentrations (50-150 mg%) of ethanol are reinforcing to the preferring rat, as evidenced by intracranial self-administration studies. Compared with nonpreferring animals, they are less affected and develop tolerance more quickly to the sedative-hypnotic effects of ethanol. Neurochemical, -anatomical and -pharmacological studies indicate innate differences between the alcohol-preferring and -nonpreferring lines in the brain limbic structures. Depending on the animal model under study, a change in the main dopaminergic pathway and/or the serotonergic, opioid, and GABAergic systems that regulate this pathway may underlie the vulnerability to the abnormal alcohol-seeking behavior in these pharmacogenetic animal models of alcoholism.