Kalynchuk L E, Kim C K, Pinel J P, Kippin T E
Department of Psychology, University of British Columbia, Vancouver, Canada.
Behav Neurosci. 1994 Feb;108(1):213-6. doi: 10.1037//0735-7044.108.1.213.
The effect of an ascending dose regimen on the development of tolerance to diazepam's anticonvulsant effect was assessed. During the 22 trials of the tolerance development phase, amygdala-kindled rats received either a series of dosage injections ranging from high (10 mg/kg), to low (1.0 mg/kg), and ascending (1.0 mg/kg and increased by 0.2-mg/kg increments to 3.0 mg/kg) or saline injections. Diazepam was administered by ip injection once every 48 hr, and each injection was followed 1 hr later by a convulsive stimulation. The ascending dose rats displayed significantly more tolerance to the anticonvulsant effect of diazepam than did the high dose, low dose, or saline rats. By contrast, both the ascending and high dose rats displayed a significant withdrawal effect (i.e., increased duration of convulsions) after the cessation of diazepam injections. Results demonstrate that administration of ascending dosages can facilitate the development of tolerance to anticonvulsant drug effects and that tolerance and withdrawal are not necessarily inextricably related.
评估了递增剂量方案对苯二氮䓬抗惊厥作用耐受性发展的影响。在耐受性发展阶段的22次试验中，杏仁核点燃大鼠接受了一系列剂量注射，从高剂量（10毫克/千克）到低剂量（1.0毫克/千克），然后递增（1.0毫克/千克，以0.2毫克/千克的增量增加至3.0毫克/千克），或者接受生理盐水注射。每48小时腹腔注射一次地西泮，每次注射1小时后进行惊厥刺激。与高剂量、低剂量或生理盐水组大鼠相比，递增剂量组大鼠对苯二氮䓬的抗惊厥作用表现出明显更高的耐受性。相比之下，在停止注射地西泮后，递增剂量组和高剂量组大鼠均表现出明显的戒断效应（即惊厥持续时间增加）。结果表明，给予递增剂量可促进对抗惊厥药物作用耐受性的发展，并且耐受性和戒断不一定必然紧密相关。
