Kuzmin A V, Gerrits M A, Van Ree J M
Laboratory of Pharmacology of Narcotics, Pavlov Medical University, St.-Petersburg, Russian Federation.
Eur J Pharmacol. 1998 Oct 9;358(3):197-202. doi: 10.1016/s0014-2999(98)00637-2.
The modulation of the reinforcing effects of cocaine by the kappa-opioid receptor antagonist, nor-binaltorphimine was studied by using the initiation of intravenous self-administration in drug-naive Wistar rats. Treatment with nor-binaltorphimine (3.0 mg/kg s.c.) 48 h before the start of the first of five daily self-administration sessions significantly decreased the intake of cocaine when offered in a threshold unit dose (30 micrograms per infusion), but had no effect on cocaine intake when it was offered in a higher unit dose (60 micrograms per infusion). It is concluded that blockade of the kappa-opioid receptor by nor-binaltorphimine may produce a rightward shift of the unit dose-response relationship of cocaine reward, thus decreasing the sensitivity to cocaine reward. These data suggest an involvement of endogenous kappa-opioid systems in the mechanisms underlying the initiation of cocaine self-administration behaviour.
通过在未接触过药物的Wistar大鼠中启动静脉自我给药，研究了κ-阿片受体拮抗剂诺-纳曲酮对可卡因强化作用的调节。在为期五天的每日自我给药疗程的第一次给药开始前48小时，给予诺-纳曲酮（3.0毫克/千克，皮下注射），当以阈剂量单位（每次输注30微克）提供可卡因时，显著降低了可卡因的摄入量，但当以更高的单位剂量（每次输注60微克）提供可卡因时，对可卡因摄入量没有影响。得出的结论是，诺-纳曲酮对κ-阿片受体的阻断可能会使可卡因奖赏的单位剂量-反应关系向右移动，从而降低对可卡因奖赏的敏感性。这些数据表明内源性κ-阿片系统参与了可卡因自我给药行为起始机制。
