Metrazol-produced impairment of passive avoidance retention specifically antagonized by anti-petit mal drugs

Abstract

In a single session, naive female 250-g Wistar rats were trained to remain for 3 min on a platform located above an electrifiable grid. During training, animals were shocked (4 mA) after they stepped down. Retention of the step-down avoidance was tested 24 h later in rats treated SC 30 min before the session with saline or a subconvulsive dose of metrazol (40 mg/kg). During the retention test no shock was delivered. The latency to step down and the time on the grid were recorded. The metrazol rats significantly failed to retain the avoidance task. Groups of six rats per dose were trained and 24 h later pretreated, 5 min before metrazol, with an IP injection of the following antiepileptics (dose range in mg/kg): Ethosuximide (20–320); trimethadione (20–320); clonazepam (0.04–0.63); sodium valproate (20–320); carbamazepine (1.25–20); phenobarbital (5–80); or diphenylhydantoin (5–80); or a high dose of haloperidol (0.16) and amphetamine (0.63). Only ethosuximide, trimethadione, and clonazepam significantly increased the latency to step down and significantly shortened the time on the grid. Sodium valproate only shortened the time spent on the grid. The results suggest that only anti-petit mal drugs antagonize the retention impairment of passive avoidance produced by metrazol.