Picrotoxin-induced disruption of bidirectional active avoidance behavior and locomotor activity

The effects of picrotoxin (0.75 and 1.5 mg/kg), an antagonist of GABA mediated chloride ion conductance changes, were examined on the acquisition and performance of a bidirectional active avoidance (BAA) response and on locomotor activity. Treatment with this agent disrupted both the acquisition and performance of this task and decreased locomotor activity. This picrotoxin-induced suppression of BAA was reversed by pretreatment with diazepam (2 mg/kg), d-amphetamine (d-AMP, 2.0 mg/kg) and lysergic acid diethylamide (LSD, 10 micrograms/kg) and was reversed partially by cinanserin (5 mg/kg) and methysergide (5 mg/kg). Picrotoxin-induced activity decreases in locomotor activity were antagonized by d-AMP, were partially reversed by LSD but were not reversed by methysergide. It is proposed that picrotoxin disrupts bidirectional active avoidance behavior by increasing the response suppressive effects of aversive stimuli and by inducing a general depression of motility.