Ability of baclofen in reducing alcohol intake and withdrawal severity: I - Preclinical evidence

Background: The similarities between the pharmacological effects of the gam ma-aminobutyric acid receptor agonist, baclofen, and the alcohol-substituti ng agent, gamma-hydroxybutyric acid, led us to investigate whether baclofen was capable of reducing (a) ethanol withdrawal syndrome in ethanol-depende nt rats and (b) voluntary ethanol intake in ethanol-preferring rats. Methods: In experiment 1, Wister rats were rendered physically dependent on ethanol by the repeated administration of intoxicating doses of ethanol fo r 6 consecutive days. Baclofen was acutely administered intraperitoneally a t 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. Results: In experiment 1. baclofen dose-dependently decreased the intensity of ethanol withdrawal signs; furthermore, 20 mg/kg of baclofen protected f rom audiogenic seizures in ethanol-withdrawn rats. In experiment 2, baclofe n selectively and dose-dependently reduced voluntary ethanol intake; a comp ensatory increase in water intake left total fluid intake virtually unchang ed. Conclusions: These results are in close agreement with those of a prelimina ry clinical study and suggest that baclofen may constitute a novel therapeu tic agent for alcoholism.