NONCONTINGENT DRUG EXPOSURE FACILITATES THE DEVELOPMENT OF CONTINGENTTOLERANCE TO THE ANTICONVULSANT EFFECTS OF ETHANOL AND DIAZEPAM IN KINDLED RATS

Tolerance to anticonvulsant drug effects on kindled convulsions can re sult from drug exposure alone, but convulsive activity during drug exp osure has a substantial facilitatory effect on tolerance development. Tolerance produced by drug exposure in the absence of a criterion resp onse (in this case convulsions) has been termed pharmacologic toleranc e (10); tolerance produced by drug exposure with concomitant performan ce of the criterion response has been termed contigent tolerance (1). The present study examines whether noncontingent drug exposure facilit ates the development of contingent tolerance to the anticonvulsant eff ects of ethanol and diazepam. Amygdala-kindled, Long-Evans rats were t reated with either ethanol (5.0 g/kg once daily for 21 days) or diazep am (5.0 mg/kg three times daily for 10 days) in the absence of convuls ive stimulation to produce pharmacologic tolerance-control rats receiv ed treatments of vehicle. Then, all of the rats were rendered continge ntly tolerant by a series of ''bidaily'' (once every 2 days) injection s (ethanol 2.0 g/kg or diazepam 2.0 mg/kg), each 1 h prior to a kindle d convulsion. The rats that had received noncontingent exposure to eth anol or diazepam developed contingent tolerance significantly faster t han the control rats. These results suggest that the mechanisms underl ying pharmacologic and contingent tolerance to anticonvulsant drug eff ects are additive. (C) 1998 Elsevier Science Inc.