Role of the GABA(B) receptor in alcohol-seeking and drinking behavior.

The present paper summarizes experimental data demonstrating the reducing effect of direct agonists and positive allosteric modulators (PAMs) of the gamma-aminobutyric acid(B) (GABA(B)) receptor on different alcohol-related behaviors. Different lines of evidence indicate that direct agonists, including baclofen, effectively suppress acquisition and maintenance of alcohol drinking behavior, relapse-like drinking, and alcohol's reinforcing, rewarding, stimulating, and motivational properties in rats and mice. More recently, the discovery of a positive allosteric modulatory binding site, together with the synthesis of in vivo effective ligands, opened a new avenue of research in GABA(B) pharmacology. Accumulating lines of evidence suggest that PAMs retain baclofen's capcity to suppress alcohol consumption and alcohol's reinforcing and motivational properties in rats; these effects occur at doses far from those producing behavioral toxicity.