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 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.
Kim
C K
CK
Department of Anatomy, University of British Columbia, Vancouver, Canada.
Kalynchuk
L E
LE
Pinel
J P
JP
Kippin
T E
TE
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001259:Ataxia / Q000139:chemically induced*; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D007696:Kindling, Neurologic; D008297:Male; D010424:Pentobarbital / Q000494:pharmacology*; D051381:Rats
D000927:Anticonvulsants; D010424:Pentobarbital