Blokhina E A, Sukhotina I A, Bespalov A Y
Laboratory of Behavioral Pharmacology, Valdman Institute of Pharmacology, Pavlov Medical University, 6/8 Lev Tolstoy St., 197089, Saint Petersburg, Russia.
Eur J Pharmacol. 2000 Oct 13;406(2):227-32. doi: 10.1016/s0014-2999(00)00689-0.
Acute pretreatment with opioid receptor agonists potentiates behavioral effects of opioid antagonists. This phenomenon was suggested to serve as an acute model of opioid dependence. Since antagonists acting at N-methyl-D-aspartate (NMDA) receptors were repeatedly shown to attenuate development, maintenance, and expression of opioid dependence, the present study evaluated the effects of competitive NMDA receptor antagonist, D-CPPene (SDZ EAA 494; 3-(2-carboxypiperazin-4-yl)-1-propenyl-1-phosphonic acid), and low-affinity channel blocker, 1-amino-3,5-dimethyl adamantane hydrochloride (memantine), on establishment of naloxone-conditioned place aversion in mice that were pre-exposed to morphine. Morphine (20 mg/kg) pretreatment significantly potentiated the ability of naloxone (0.01-0.3 mg/kg) to produce place aversion. The place aversion produced by naloxone (0.1 mg/kg) was attenuated by D-CPPene (1 and 3 mg/kg but not 0.1 or 0.3 mg/kg) when it was administered 3.5 h after morphine (0.5 h prior to conditioning trial with naloxone) but not 0.5 h prior to morphine. Memantine (1-10 mg/kg) had no effect under any treatment condition (0.5 h prior to morphine, simultaneously with morphine, 2 or 3.5 h after morphine). Thus, the ability of NMDA receptor antagonist to affect development and/or expression of morphine dependence may not be a good predictor of their effects on establishment of morphine-potentiated naloxone-conditioned place aversion.
用阿片受体激动剂进行急性预处理可增强阿片拮抗剂的行为效应。这一现象被认为可作为阿片类药物依赖的急性模型。由于作用于N-甲基-D-天冬氨酸（NMDA）受体的拮抗剂反复显示可减弱阿片类药物依赖的发展、维持和表达，本研究评估了竞争性NMDA受体拮抗剂D-CPPene（SDZ EAA 494；3-(2-羧基哌嗪-4-基)-1-丙烯基-1-膦酸）和低亲和力通道阻滞剂盐酸1-氨基-3,5-二甲基金刚烷（美金刚）对预先接触吗啡的小鼠建立纳洛酮条件性位置厌恶的影响。吗啡（20mg/kg）预处理显著增强了纳洛酮（0.01 - 0.3mg/kg）产生位置厌恶的能力。当在吗啡给药后3.5小时（在用纳洛酮进行条件试验前0.5小时）给予D-CPPene（1和3mg/kg，但不是0.1或0.3mg/kg）时，可减弱纳洛酮（0.1mg/kg）产生的位置厌恶，但在吗啡给药前0.5小时给予则无此作用。美金刚（1 - 10mg/kg）在任何处理条件下（吗啡给药前0.5小时、与吗啡同时给药、吗啡给药后2或3.5小时）均无作用。因此，NMDA受体拮抗剂影响吗啡依赖的发展和/或表达的能力可能并非其对吗啡增强的纳洛酮条件性位置厌恶建立作用的良好预测指标。
