Title | Tolerance to the anticonvulsant and ataxic effects of pentobarbital: effect of an ascending-dose regimen. |
Publication Type | Journal Article |
Year of Publication | 1995 |
Authors | Kim CK, Kalynchuk LE, Pinel JP, Kippin TE |
Journal | Pharmacol Biochem Behav |
Volume | 52 |
Issue | 4 |
Pagination | 825-9 |
Date Published | 1995 Dec |
ISSN | 0091-3057 |
Keywords | Animals, Anticonvulsants, Ataxia, Dose-Response Relationship, Drug, Drug Tolerance, Kindling, Neurologic, Male, Pentobarbital, Rats |
Abstract | We assessed the effect of an ascending-dose regimen on the development of tolerance to the anticonvulsant and ataxic effects of pentobarbital in four groups of amygdala-kindled rats. Each rat received 20 bidaily (one every 48 h) trials in which an intraperitoneal (IP) pentobarbital or vehicle injection was delivered 1 h before a convulsive amygdala stimulation. On each trial, the rats in the three pentobarbital groups received either a high dose (50 mg/kg), a low dose (10mg/kg), or ascending 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 its anticonvulsant effect; the rats in the vehicle group received saline. The rats in the ascending-dose condition displayed significantly more tolerance to the anticonvulsant effect of pentobarbital than did the 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 ascending-dose regimens on the development of tolerance to the anticonvulsant effect of benzodiazepines, and show that the facilitatory effect of ascending-dose regimens does not extend to all drug effects. |
Alternate Journal | Pharmacol. Biochem. Behav. |
PubMed ID | 8587926 |