THE ROLE OF GABA-B RECEPTORS IN MEDIATING THE STIMULATORY EFFECTS OF ETHANOL IN MICE

Recently, the GABA(B) receptor antagonist phaclofen has been shown to attenuate the stimulation of locomotor activity induced by ethanol (Al lan and Harris 1989). In the present study, the effects of a range of recently developed GABA(B) receptor antagonists (phaclofen, 2-hydroxys aclofen, beta-phenyl-beta-alanine, CGP 35348) and the GABA(B) receptor agonist baclofen, were studied for their ability to block the locomot or stimulation induced by a low dose of ethanol administered IP to mic e (1.75 g/kg). Results showed that phaclofen, 2-hydroxysaclofen, BPBA and baclofen all dose-dependently decreased ethanol-induced locomotor activity, and, of these, baclofen and BPBA did so at doses which did n ot attenuate locomotor activity when administered alone. CGP 35348 had no effect on the activity produced by ethanol. The action of baclofen on ethanol-induced activity appeared to be GABA(B) receptor mediated, as the effects were stereospecific and were reversed by the antagonis t, CGP 35348. However phaclofen, 2-hydroxysaclofen and BPBA failed to reverse the effects of baclofen. These results suggest that the GABA(B ) receptor may modulate locomotor stimulation induced by low doses of ethanol, and furthermore, that agonist, rather than antagonist activit y at the GABA(B) receptor is responsible for this reduction. The GABA( B) receptor subtype responsible for modulating the effects of ethanol may have properties different from those GABA(B) receptors characteris ed to date.