McMahon Lance R, Sell Stacy L, France Charles P
Department of Pharmacology, The University of Texas Health Science Center, San Antonio, Texas 78229-3900, USA.
J Pharmacol Exp Ther. 2004 Jan;308(1):111-9. doi: 10.1124/jpet.103.058917. Epub 2003 Oct 20.
Monoaminergic drugs can modify opioid withdrawal in nonhumans, and cocaine is reported to attenuate opioid withdrawal in humans. Drug discrimination was used to examine whether s.c. cocaine or other indirect-acting monoamine agonists attenuate morphine (3.2 mg/kg/day) withdrawal induced by naltrexone and by 27 h of morphine deprivation. Naltrexone-precipitated withdrawal was attenuated not only by morphine but also by cocaine, amphetamine, and imipramine. However, reversal of naltrexone-precipitated withdrawal was greater for morphine than for any of the indirect-acting monoamine agonists. Attenuation of the naltrexone discriminative stimulus by indirect-acting monoamine agonists was pharmacologically selective insofar as drugs lacking affinity for monoamine transporters (ketamine and triazolam) were without effect. Twenty-seven hours of morphine deprivation occasioned naltrexone-lever responding and decreased response rate, and both effects were reversed by morphine, cocaine, and amphetamine and not by imipramine, desipramine, ketamine, and triazolam. Thus, indirect-acting monoamine agonists attenuate some (e.g., discriminative) aspects of naltrexone-precipitated withdrawal, whereas only indirect-acting agonists with high affinity for dopamine transporters attenuate deprivation-induced withdrawal. These results suggest that dopamine is differentially involved in naltrexone- and deprivation-induced withdrawal and support the notion that opioid-dependent individuals use stimulants, in part, to attenuate withdrawal.
单胺能药物可改变非人类动物的阿片类戒断反应，据报道可卡因可减轻人类的阿片类戒断反应。采用药物辨别试验来检测皮下注射可卡因或其他间接作用的单胺类激动剂是否能减轻由纳曲酮和27小时吗啡剥夺所诱发的吗啡（3.2毫克/千克/天）戒断反应。纳曲酮诱发的戒断反应不仅可被吗啡减轻，还可被可卡因、苯丙胺和丙咪嗪减轻。然而，对于吗啡而言，纳曲酮诱发的戒断反应的逆转程度大于任何一种间接作用的单胺类激动剂。间接作用的单胺类激动剂对纳曲酮辨别刺激的减轻在药理学上具有选择性，因为对单胺转运体缺乏亲和力的药物（氯胺酮和三唑仑）没有效果。27小时的吗啡剥夺引发了纳曲酮杠杆反应并降低了反应率，这两种效应均可被吗啡、可卡因和苯丙胺逆转，而不能被丙咪嗪、地昔帕明、氯胺酮和三唑仑逆转。因此，间接作用的单胺类激动剂可减轻纳曲酮诱发的戒断反应的某些方面（如辨别），而只有对多巴胺转运体具有高亲和力的间接作用激动剂才能减轻剥夺诱发的戒断反应。这些结果表明，多巴胺在纳曲酮诱发的和剥夺诱发的戒断反应中所起的作用不同，并支持了阿片类药物依赖个体部分地使用兴奋剂来减轻戒断反应这一观点。
