Schulteis G, Yackey M, Risbrough V, Koob G F
Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Pharmacol Biochem Behav. 1998 Jul;60(3):727-31. doi: 10.1016/s0091-3057(98)00034-3.
Withdrawal from opiates and other drugs of abuse in human addicts is associated with a state of anxiety that may be of motivational relevance for the maintenance of drug addiction. Previous attempts with rats to model the anxiogenic-like effects of opiate withdrawal using the elevated plus-maze have met with mixed success. The current study sought to determine whether spontaneous and naloxone-precipitated opiate withdrawal could be observed reliably in rats made dependent on morphine through implantation of two morphine pellets (75 mg morphine base each). Seventy-two hours after implantation of either morphine or placebo pellets, rats were tested in the elevated plus-maze. In Experiment 1, pellets were removed 8 or 12 h prior to test; results indicated an anxiogenic-like effect (reduction in time spent in the open arms) of opiate withdrawal at 8 but not 12 h postpellet removal. In Experiment 2, pellets were not removed, but withdrawal was precipitated with naloxone (0.003-0.03 mg/kg s.c.). Naloxone dose dependently precipitated a reduction in exploration of the open arms of the plus-maze. The results suggest that both spontaneous and precipitated withdrawal from continuous morphine administration via pellet implantation result in demonstrable anxiogenic-like effects in the plus-maze.
人类成瘾者停用阿片类药物及其他滥用药物时会出现焦虑状态，这种焦虑状态可能与药物成瘾的维持存在动机关联。此前用大鼠通过高架十字迷宫模拟阿片类药物戒断的致焦虑样效应的尝试，结果喜忧参半。当前研究旨在确定，通过植入两枚吗啡丸（每枚含75毫克吗啡碱）使大鼠对吗啡产生依赖后，是否能可靠观察到自发及纳洛酮诱发的阿片类药物戒断反应。在植入吗啡丸或安慰剂丸72小时后对大鼠进行高架十字迷宫测试。实验1中，在测试前8小时或12小时取出药丸；结果表明，在取出药丸后8小时而非12小时出现了阿片类药物戒断的致焦虑样效应（在开放臂停留时间减少）。实验2中，未取出药丸，但用纳洛酮（0.003 - 0.03毫克/千克皮下注射）诱发戒断反应。纳洛酮剂量依赖性地导致大鼠对十字迷宫开放臂的探索减少。结果表明，通过药丸植入持续给予吗啡后，自发及诱发的戒断反应均会在十字迷宫中产生明显的致焦虑样效应。
