Kippin T E, Pinel J J, Kornecook T J, Kalynchuk L E
Center for Studies in Behavioral Neurobiology, Department of Psychology, Concordia University, Montréal, Québec, Canada.
Pharmacol Biochem Behav. 1998 Sep;61(1):143-8. doi: 10.1016/s0091-3057(98)00081-1.
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.
对抗惊厥药物作用于点燃惊厥产生的耐受性可能仅由药物暴露引起，但药物暴露期间的惊厥活动对耐受性发展有显著的促进作用。在没有标准反应（在这种情况下为惊厥）时由药物暴露产生的耐受性被称为药理学耐受性（10）；在伴有标准反应时由药物暴露产生的耐受性被称为条件耐受性（1）。本研究考察非条件性药物暴露是否会促进对乙醇和地西泮抗惊厥作用的条件耐受性的发展。对杏仁核点燃的Long-Evans大鼠，在无惊厥刺激的情况下用乙醇（5.0 g/kg，每日一次，共21天）或地西泮（5.0 mg/kg，每日三次，共10天）进行处理以产生药理学耐受性——对照大鼠接受赋形剂处理。然后，通过一系列“每两天一次”（每2天一次）的注射（乙醇2.0 g/kg或地西泮2.0 mg/kg），在每次点燃惊厥前1小时，使所有大鼠产生条件耐受性。接受过乙醇或地西泮非条件性暴露的大鼠比对照大鼠显著更快地产生了条件耐受性。这些结果表明，对抗惊厥药物作用的药理学耐受性和条件耐受性的潜在机制是相加的。
