Gamma-hydroxybutyric acid reducing effect on ethanol intake: evidence in favour of a substitution mechanism.

Experiment 1 in the present study investigated the time course and dose range of gamma-hydroxybutyric acid (GHB) to reduce voluntary ethanol intake in selectively bred Sardinian ethanol-preferring (sP) rats. Ethanol (10%, v/v) and tap water were offered under the two-bottle free choice regimen with unlimited access. GHB (200, 300, and 400 mg/kg, i.p.) was administered 15 20 min prior to the start of the dark phase of the light-dark cycle. Ethanol and water intakes were recorded at different time intervals during the dark phase. GHB significantly reduced ethanol intake at doses of 300 and 400 mg/kg; statistical significance occurred only at the 15-min and 30-min observation times. The GHB dose of 300 mg/kg was devoid of any sedative effect, as demonstrated in Experiment 2 by the lack of any impairment of spontaneous locomotor activity. Finally, this dose of GHB was also found to exert a robust anxiolytic effect in sP rats tested on the elevated plus maze (Experiment 3). Collectively, the results of the present study demonstrate that a non-sedative and anxiolytic dose of GHB effectively reduced voluntary ethanol intake in sP rats. The rapid onset of the reducing effect of GHB on ethanol intake, as well as its anxiolytic effect, are discussed in terms of adding further support to the hypothesis that GHB may control alcohol craving and consumption in humans by substituting for ethanol's reinforcing effects.