DO GABA(B) RECEPTORS HAVE A ROLE IN CAUSING BEHAVIORAL HYPEREXCITABILITY, BOTH DURING ETHANOL WITHDRAWAL AND IN NAIVE MICE

The effects of the GABA(B) agonist baclofen and the GABA(B) antagonist CGP35348 were examined on the behavioural hyperexcitability which is seen on cessation of chronic ethanol treatment. When baclofen was give n to mice of the TO strain after withdrawal from ethanol inhalation, t here was evidence of increased hyperexcitability with one dose, 2.5 mg /kg, but no significant change was seen with other doses, 1.25 and 10 mg/kg. When given after withdrawal from a liquid diet containing ethan ol, baclofen, 10 mg/kg, produced a large, but short lasting, increase in the ratings of hyperexcitability during the withdrawal period. This effect was significantly decreased when the antagonist CGP35348, 300 mg/kg, was given with baclofen 10 mg/kg. When the antagonist was given alone at 300 mg/kg it significantly decreased the hyperexcitability d uring ethanol withdrawal. Increases in the ratings of hyperexcitabilit y were seen when baclofen was given to control mice, which had not rec eived ethanol, and these effects were significant, so the effects duri ng ethanol withdrawal were not confined to that syndrome. CGP35348 dec reased the behavioural ratings in control animals, and blocked the eff ects of baclofen 10 mg/kg. When the effects of the compounds on sponta neous locomotor activity in control mice were measured, this parameter was decreased both by baclofen and by CGP35348, at does which were ef fective in altering the handling-induced behaviour.