Reducing effect of the positive allosteric modulator of the GABA(B) receptor, GS39,783, on alcohol self-administration in alcohol-preferring rats.

ABSTRACT

RATIONALE AND OBJECTIVES: The positive allosteric modulator of the GABA(B) receptor, GS39,783, has recently been found to suppress acquisition and maintenance of alcohol drinking behavior in selectively bred Sardinian alcohol-preferring (sP) rats exposed to the standard, homecage two-bottle "alcohol vs water" choice regimen. The present study was designed to extend the characterization of the "anti-alcohol" effects of GS39,783 to oral self-administration of alcohol under an operant procedure. MATERIALS AND METHODS: Two separate groups of male sP rats were trained to lever-press (on an FR4 schedule) to orally self-administer alcohol (15%, v/v) or sucrose (0.3%, w/v) in daily 30-min sessions. Once lever-pressing behavior reached stable levels, the effect of GS39,783 (0, 25, 50, and 100 mg/kg, i.g.) on responding for alcohol and sucrose was determined. RESULTS: Pretreatment with GS39,783 resulted in a significant, dose-dependent reduction in responding for alcohol; at the dose of 100 mg/kg GS39,783, the number of lever responses for alcohol was reduced by approximately 50% in comparison to vehicle-treated rats. The effect of GS39,783 on alcohol self-administration was specific, as responding for sucrose was completely unaffected by pretreatment with GS39,783. CONCLUSIONS: These data demonstrate the capability of GS39,783 to attenuate the reinforcing properties of alcohol in alcohol-preferring rats. These data constitute a further piece of experimental evidence in support of the hypothesized role for the GABA(B) receptor in the control of alcohol drinking and reinforcement.