Differences in the development of tolerance to two anticonvulsant benzodiazepines in the amygdaloid kindled rat

The effects of chronic treatment with two benzodiazepines were studied on kindled amygdaloid seizures in rats. Clobazam (4 mg kg-1), clonazepam (0.3 mg kg-1) or vehicle (1 mL kg-1) was administered, by intraperitoneal injection, to fully kindled rats twice daily for nineteen days. Each rat was electrically stimulated 30 min after the morning dose on alternate days of treatment. Tolerance developed rapidly to the anticonvulsant effects of clobazam after only three days of treatment, following which only a small residual protection was maintained. Tolerance to clonazepam developed gradually over the course of the experiment, although this effect was relatively minor.