The similarities between the pharmacological effects of the γ-aminobutyric acid receptor agonist, baclofen, and the alcohol-substituting agent, γ-hydroxybutyric acid, led us to investigate whether baclofen was capable of reducing (a) ethanol withdrawal syndrome in ethanol-dependent rats and (b) voluntary ethanol intake in ethanol-preferring rats.
In experiment 1, Wistar rats were rendered physically dependent on ethanol by the repeated administration of intoxicating doses of ethanol for 6 consecutive days. Baclofen was acutely administered intraperitoneally at doses of 10, 20, and 40 mg/kg. In experiment 2, baclofen (0, 2.5, 5, and 10 mg/kg, intraperitoneally) was administered once a day for 14 consecutive days to ethanol-preferring sP rats that had continuous access to ethanol (10%, v/v) and water under the two-bottle free choice regimen.
In experiment 1, baclofen dose-dependently decreased the intensity of ethanol withdrawal signs; furthermore, 20 mg/kg of baclofen protected from audiogenic seizures in ethanol-withdrawn rats. In experiment 2, baclofen selectively and dose-dependently reduced voluntary ethanol intake; a compensatory increase in water intake left total fluid intake virtually unchanged.
These results are in close agreement with those of a preliminary clinical study and suggest that baclofen may constitute a novel therapeutic agent for alcoholism.