Ability of Baclofen in Reducing Alcohol Intake and Withdrawal Severity: I—Preclinical Evidence

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Abstract
Background: 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.Methods: 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.Results: 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intensity of ethanol withdrawal signs; furthermore, 20 mg/kg of baclofen protected from audiogenic seizures in ethanol‐withdrawn rats.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.Conclusions: 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.