Suppression of ethanol-induced locomotor stimulation by GABA-like drugs

Ethanol (2.4 g/kg) was given intraperitoneally to mice and was found to cause a marked increase in spontaneous locomotor activity. When mice were pretreated with low doses of agents which mimic or augment the action of GABA (gamma-hydroxybutyric acid, baclophen, or aminooxyacetic acid) the ethanol-induced locomotor stimulation was completely eliminated; Baclophen (10 mg/kg) was found to cause an initial increase followed by a later decrease in synthesis of catecholamines, as measured by the accumulation of dopa after inhibition of central aromatic L-amino acid decarboxylase, in dopamine-rich areas of rat brain. These data are consistent with previous findings that baclophen, as well as other agents which enhance the activity of GABA systems, reduce the firing of dopamine neurons, thus causing enhanced synthesis of dopamine via feedback mechanisms. These findings also indicate a potential interaction between GABA-like drugs and alcohol in man, and may be of heuristic value in the treatment of chronic alcoholism. The possibility that the mechanism of the inhibition of ethanol-induced locomotor stimulation by GABA-like drugs may be due to a selective interference with ethanol-induced dopamine release is discussed.