Noncontingent drug exposure facilitates the development of contingent tolerance to the anticonvulsant effects of ethanol and diazepam in kindled rats.

TitleNoncontingent drug exposure facilitates the development of contingent tolerance to the anticonvulsant effects of ethanol and diazepam in kindled rats.
Publication TypeJournal Article
Year of Publication1998
AuthorsKippin TE, Pinel JJ, Kornecook TJ, Kalynchuk LE
JournalPharmacol Biochem Behav
Volume61
Issue1
Pagination143-8
Date Published1998 Sep
ISSN0091-3057
KeywordsAnimals, Anticonvulsants, Brain, Central Nervous System Depressants, Diazepam, Drug Tolerance, Ethanol, Kindling, Neurologic, Male, Movement, Rats
Abstract

Tolerance to anticonvulsant drug effects on kindled convulsions can result from drug exposure alone, but convulsive activity during drug exposure has a substantial facilitatory effect on tolerance development. Tolerance produced by drug exposure in the absence of a criterion response (in this case convulsions) has been termed pharmacologic tolerance (10); tolerance produced by drug exposure with concomitant performance of the criterion response has been termed contingent tolerance (1). The present study examines whether noncontingent drug exposure facilitates the development of contingent tolerance to the anticonvulsant effects of ethanol and diazepam. Amygdala-kindled, Long-Evans rats were treated with either ethanol (5.0 g/kg once daily for 21 days) or diazepam (5.0 mg/kg three times daily for 10 days) in the absence of convulsive stimulation to produce pharmacologic tolerance--control rats received treatments of vehicle. Then, all of the rats were rendered contingently tolerant by a series of "bidaily" (once every 2 days) injections (ethanol 2.0 g/kg or diazepam 2.0 mg/kg), each 1 h prior to a kindled convulsion. The rats that had received noncontingent exposure to ethanol or diazepam developed contingent tolerance significantly faster than the control rats. These results suggest that the mechanisms underlying pharmacologic and contingent tolerance to anticonvulsant drug effects are additive.

Alternate JournalPharmacol. Biochem. Behav.
PubMed ID9715816