TOLERANCE TO THE ANTICONVULSANT AND ATAXIC EFFECTS OF PENTOBARBITAL -EFFECT OF AN ASCENDING-DOSE REGIMEN

We assessed the effect of an ascending-dose regimen on the development of tolerance to the anticonvulsant and ataxic effects of pentobarbita l in four groups of amygdala-kindled rats. Each rat received 20 bidail y (one every 48 h) trials in which an intraperitoneal (IF) pentobarbit al or vehicle injection was delivered 1 h before a convulsive amygdala stimulation. On each trial, the rats in the three pentobarbital group s received either a high dose (50 mg/kg), a low dose (10 mg/kg), or as cending doses of pentobarbital that began at 10 mg/kg and increased to as high as 26 mg/kg by 1 mg/kg increments as tolerance developed to i ts anticonvulsant effect; the rats in the vehicle group received salin e. The rats in the ascending-dose condition displayed significantly mo re tolerance to the anticonvulsant effect of pentobarbital than did th e other rats; in contrast, the high-dose rats displayed more tolerance to the ataxic effect of pentobarbital than did the other rats. These findings extend previous reports of the facilitatory effect of ascendi ng-dose regimens on the development of tolerance to the anticonvulsant effect of benzodiazepines, and show that the facilitatory effect of a scending-dose regimens does not extend to all drug effects.