期刊
ALCOHOL
卷 43, 期 7, 页码 555-558出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.alcohol.2009.09.030
关键词
GABA(B) receptor; Direct agonists; Baclofen; Positive allosteric modulators; Alcohol intake; Operant alcohol self-administration; Reinforcing and motivational properties of alcohol; Alcohol-preferring rats
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 GABAB pharmacology. Accumulating lines of evidence suggest that PAMs retain baclofen's capcity to supprcss alcohol consumption and alcohol's reinforcing and motivational properties in rats; these effects occur at doses far from those producing behavioral toxicity. (C) 2009 Elsevier Inc. All rights reserved.
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