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.
Maccioni
Paola
P
C.N.R. Institute of Neuroscience, I-09126 Cagliari, Italy.
Colombo
Giancarlo
G
D000428:Alcohol Drinking / Q000523:psychology*; D000437:Alcoholism / Q000188:drug therapy / Q000209:etiology*; D000494:Allosteric Regulation; D000818:Animals; D001418:Baclofen / Q000627:therapeutic use; D003517:Cyclopentanes / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology; D006801:Humans; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D018080:Receptors, GABA-B / Q000502:physiology*
D003517:Cyclopentanes; D018757:GABA Modulators; C478058:N,N'-dicyclopentyl-2-methylsulfanyl-5-nitro-pyrimidine-4,6-diamine; D011743:Pyrimidines; D018080:Receptors, GABA-B; D001418:Baclofen