Valproate potentiates and picrotoxin antagonizes the anxiolytic action of ethanol in a nonshock conflict task.

The purpose of this study was to examine the effects of the indirect GABA agonist valproate and the indirect GABA antagonist picrotoxin on the anxiolytic (anti-conflict) activity of ethanol in a behavioral conflict task that does not employ electroshock. This task (negative contrast) quantifies how animals respond to an abrupt, unexpected reduction in reward. Treatment with valproate alone did not elevated depressed behavior engendered by abrupt reduction in reward. However, when administered together with a sub-effective dose of ethanol (0.5 g/kg), valproate (50-200 mg/kg) dose-dependently potentiated the anxiolytic action of ethanol. Picrotoxin (2 mg/kg) antagonized the anxiolytic effects of a larger dose of ethanol (1.0 g/kg) given alone, as well as the ability of valproate to enhance the anxiolytic effects of smaller dose of ethanol (0.5 g/kg). As such, these data support a role for GABA in mediating the anxiolytic activity of ethanol.