France C P, Woods J H
Department of Psychology, University of Michigan, Ann Arbor.
J Pharmacol Exp Ther. 1988 Feb;244(2):599-605.
The ability of acute morphine injections to augment discriminative stimulus effects and rate-decreasing effects of opioid antagonists was examined in pigeons trained to discriminate among i.m. injections of morphine (5.6 mg/kg), saline and naltrexone (10.0 mg/kg). A single injection of 10.0 or 32.0 mg/kg of morphine 24 hr before naltrexone produced 3- and 10-fold decreases, respectively, in the dose of naltrexone required for complete generalization. When morphine (10.0-100.0 mg/kg) was administered 48 hr before naltrexone, pigeons were not more sensitive to naltrexone as a discriminative stimulus but continued to be more sensitive to the rate-decreasing effects of naltrexone. Conditions that produced the largest increase in sensitivity to the discriminative stimulus effects of naltrexone (32.0 mg/kg of morphine 24 hr before the session) also increased sensitivity to the discriminative stimulus effects and rate-decreasing effects of naloxone, but did not affect the discriminative stimulus effects of diprenorphine, nalorphine or morphine. Increases in sensitivity to the discriminative stimulus effects of naltrexone and naloxone after single injections of morphine approached in magnitude the increases reported previously in pigeons treated chronically (once/daily) with large doses of morphine. However, the lack of generalization to naltrexone after pretreatment with still larger doses of morphine, as well as the failure of nalorphine and diprenorphine to substitute for naltrexone as discriminative stimuli under conditions in which sensitivity to naltrexone was increased, support the view that naltrexone does not produce its discriminative stimulus effects in nondependent animals exclusively through an opioid antagonistic action. The results suggest that morphine induced, acute supersensitivity to the discriminative stimulus effects of naltrexone differs from the supersensitivity to antagonists observed during chronic morphine treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
在经过训练以区分肌肉注射吗啡（5.6毫克/千克）、生理盐水和纳曲酮（10.0毫克/千克）的鸽子中，研究了急性注射吗啡增强阿片类拮抗剂辨别刺激效应和降低反应率效应的能力。在纳曲酮注射前24小时单次注射10.0或32.0毫克/千克吗啡，分别使完全泛化所需的纳曲酮剂量降低了3倍和10倍。当在纳曲酮注射前48小时给予吗啡（10.0 - 100.0毫克/千克）时，鸽子对纳曲酮作为辨别刺激并不更敏感，但对纳曲酮降低反应率的效应仍更敏感。导致对纳曲酮辨别刺激效应敏感性增加最大的条件（在实验前24小时注射32.0毫克/千克吗啡），也增加了对纳洛酮辨别刺激效应和降低反应率效应的敏感性，但不影响二丙诺啡、烯丙吗啡或吗啡的辨别刺激效应。单次注射吗啡后对纳曲酮和纳洛酮辨别刺激效应敏感性的增加幅度，接近先前报道的长期（每日一次）用大剂量吗啡治疗的鸽子的增加幅度。然而，用更大剂量吗啡预处理后对纳曲酮缺乏泛化，以及在对纳曲酮敏感性增加的条件下烯丙吗啡和二丙诺啡不能替代纳曲酮作为辨别刺激，支持了纳曲酮并非仅通过阿片类拮抗作用在非依赖动物中产生其辨别刺激效应的观点。结果表明，吗啡诱导的对纳曲酮辨别刺激效应的急性超敏反应，不同于慢性吗啡治疗期间观察到的对拮抗剂的超敏反应。（摘要截断于250字）
