Do the effects of chronic ethanol exposure in animal studies translate to humans? Behavioral adaptations to ethanol in human beings mimic those observed in animal models. Further, GABAergic neurotransmission is important for many behavioral actions of ethanol and several studies in human alcoholics have highlighted changes in GABAA receptor function and plasticity that resemble the adaptations found in animal models of ethanol dependence. For instance, human alcoholics exhibit ethanol tolerance and benzodiazepine and barbiturate cross-tolerance (Volkow et al. 1993; Woo and Greenblatt 1979). Early studies conducted in post-mortem human brains have suggested the involvement of GABAA receptors: [3H]muscimol binding density is greater in alcoholic cerebral cortex (Tran et al. 1981) and superior frontal gyrus of non-cirrhotic alcoholics (Dodd et al. 1992) compared to healthy controls. Increases, decreases, or no changes in benzodiazepine binding have been reported in several studies of postmortem human alcoholics (Dodd 1995; Dodd et al. 1992; Freund and Ballinger 1988).
