THE EFFECTS OF GABA(B) LIGANDS ON ALCOHOL-WITHDRAWAL IN MICE

Recent research suggests that the GABA(B) receptor may mediate some of the acute effects of alcohol, but little is known of its involvement in alcohol withdrawal. Mice made dependent on alcohol exhibited tremor and tail arch when consumption ceased. Diazepam dose-dependently atte nuated both tremor and tail arch, whereas baclofen had no effect on ei ther of these two withdrawal symptoms. However, baclofen dose-dependen tly induced convulsant behaviour in the withdrawing mice, and this was significantly attenuated by the GABA(B) antagonists phaclofen (50 mg/ kg) and CGP 35348 (300 mg/kg), but not BPBA (50 mg/kg). Phaclofen, BPB A, and CGP 35348, when administered alone and in combination with a si ngle dose of baclofen, did have an effect on tremor, although the magn itude was small in comparison to that seen with diazepam. It appears t hat the GABA(B) receptor may play a role in mediating convulsions duri ng alcohol withdrawal, and that in this system baclofen is proconvulsa nt.