Gamma-hydroxybutyric acid versus alcohol preference in Sardinian alcohol-preferring rats

Previous experiments demonstrated that the selectively bred Sardinian alcohol-preferring (sP) rats possess a genetically based proclivity to consume pharmacologically relevant doses of gamma-hydroxybutyric acid (GHB). The present study was aimed at comparing the reinforcing properties of GHB and ethanol, measuring the propensity of sP rats to consume GHB and ethanol when both drugs were concomitantly available. Initially, two groups of sP rats (ethanol-naive and ethanol-experienced, respectively) were forced to consume GHB in order to help them discover the reinforcing properties, which could then prevail over the unpleasant taste of the GHB solution. Subsequently GHB (at concentrations increasing from 1 to 6% w/v) was offered in free choice with water and all rats consumed pharmacologically relevant amounts of GHB. Finally, under the free-choice regimen between GHB (presented to each rat at its preferred concentration), ethanol and water, daily ethanol intake averaged approximately 6 g/kg (i.e. the amount of ethanol usually consumed by sP rats), whereas GHB intake declined by approximately 75%. In the few rats showing a high intake of GHB, ethanol intake was not altered. No difference in GHB drinking behaviour was ever recorded between ethanol-naive and ethanol-experienced rats. The results of the present study demonstrate that freely available GHB is not capable of altering ethanol preference and consumption in sP rats and suggest that the postulated reciprocal substitutability of the two drugs does not completely include the reinforcing properties, at least in sP rats and when oral self-administration of GHB is considered. The results also provide a model of the low abuse liability of GHB observed in human alcoholics.