Mechanism of the antialcohol effect of gamma-hydroxybutyric acid

Treatment with gamma-hydroxybutyric acid has been reported to effectively d ecrease alcohol craving and consumption as well as alcohol withdrawal sympt oms in alcoholics. We describe the results of animal studies demonstrating the ability of gamma-hydroxybutyric acid to reduce (1) the severity of etha nol withdrawal signs in rats rendered physically dependent on ethanol and ( 2) voluntary ethanol intake in selectively bred Sardinian alcohol-preferrin g rats. Furthermore, we review experimental data suggesting that gamma-hydr oxybutyric acid and ethanol have several pharmacological effects in common. Relevant similarities are: (1) stimulation of firing rate of dopaminergic neurons and dopamine release in specific rat brain areas; (2) development o f cross-tolerance to the motor-impairing effects: after repeated administra tion in rats; 3) abuse potential, as indicated by self-administration of ph armacologically relevant doses of gammahydroxybutyric acid in rats and mice : (4) induction of anxiolytic effects in rats; and (5) induction of similar discriminative stimulus effects, as evidenced by symmetrical generalizatio n in a drug discrimination study in rats. These lines of evidence are discu ssed in relation to gamma-hydroxybutyric acid exerting its antialcohol effe cts by a substitution mechanism. (C) 2000 Elsevier Science Inc. All rights re served.