Ability of baclofen in reducing alcohol intake and withdrawal severity: I--Preclinical evidence.
BACKGROUND
The similarities between the pharmacological effects of the gamma-aminobutyric acid receptor agonist, baclofen, and the alcohol-substituting agent, gamma-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intensity of ethanol withdrawal signs; furthermore, 20 mg/kg of baclofen protected from audiogenic seizures in ethanol-withdrawn rats.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.
Colombo
G
G
CNR Center for Neuropharmacology, Bernard B. Brodie Department of Neuroscience, University of Cagliari, Italy. colomb@unica.it
Agabio
R
R
Carai
M A
MA
Lobina
C
C
Pani
M
M
Reali
R
R
Addolorato
G
G
Gessa
G L
GL
D000428:Alcohol Drinking / Q000517:prevention & control* / Q000523:psychology; D000437:Alcoholism / Q000523:psychology; D000818:Animals; D001418:Baclofen / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D000431:Ethanol / Q000009:adverse effects*; D018755:GABA Agonists / Q000494:pharmacology*; D008297:Male; D009042:Motivation; D051381:Rats; D017208:Rats, Wistar; D013375:Substance Withdrawal Syndrome / Q000517:prevention & control* / Q000523:psychology
D018755:GABA Agonists; D000431:Ethanol; D001418:Baclofen