GABA(A) receptor modulation of the rewarding and aversive effects of ethanol

Ethanol has been shown to exert many of its biochemical and behavioral effects through an interaction with the gamma-aminobutyric acid (GABA) receptor system. This review focuses on a subset of studies that has used self-administration, as well as place and taste conditioning, procedures to investigate a role for the GABA(A) receptor system in modulating the rewarding and aversive effects of ethanol. Potential advantages and disadvantages of each procedure are also discussed. A significant amount of evidence supports the suggestion that GABA(A) receptors are important modulators of the motivational effects of ethanol, although most of the findings have been obtained from studies examining oral ethanol self-administration. Relatively fewer studies have investigated ethanol place and taste conditioning. All self-administration studies reviewed used rats, whereas most conditioning studies used mice. Results of these studies show that GABA(A) antagonists and inverse agonists reduce ethanol self-administration under limited-access conditions. The effect of GABA(A) agonists on ethanol self-administration is less clear due to their bidirectional effects. GABA(A) receptor antagonists have been shown to increase ethanol-induced conditioned place preference and conditioned taste aversion in mice and decrease ethanol-induced conditioned taste aversion in rats. Issues related to interpretation and integration of these findings across models and species are considered. The integration of data from self-administration and conditioning procedures is necessary to define the role of GABA(A) receptors in modulating the rewarding and aversive effects of ethanol and may lead to the development of pharmacotherapies that target GABA(A) receptors to treat alcoholism in human beings.