Laboratory of Psychopharmacology, Department of Pharmacology, Universidade Federal de Santa Catarina, Campus Universitário Trindade, 88049-900, Florianopolis, SC, Brazil,
Psychopharmacology (Berl). 2014 Apr;231(7):1417-25. doi: 10.1007/s00213-013-3331-2. Epub 2013 Nov 19.
Drug addicts constantly relapse to drug seeking after recall of memories linked to the drug experience. It is believed that a successful application of therapies that block memory reconsolidation may end the continuous cycle of drug relapse.
The purpose of this study is to investigate whether modulation of the endocannabinoid system would impact the reconsolidation of opioid-related hedonic memories in rats previously paired to morphine context.
Male Wistar rats were trained to acquire a morphine-conditioned place preference (CPP). One week later, morphine-CPP memory was reactivated by a brief exposure to a drug-paired context. Immediately after the memory reactivation session, independent groups of morphine-trained rats received a single subcutaneous injection of different doses of cannabinoid CB1 receptor antagonist rimonabant, CB2-selective antagonist AM630, potent CB1/CB2 agonist WIN 55,212-2, inhibitor of enzyme fatty acid amide hydrolase URB597, or vehicle. Morphine-CPP was retested 1 and 2 weeks after reactivation.
Blockade of CB1 (but not CB2) cannabinoid receptors impaired CPP reconsolidation of morphine-CPP at both tests 1 and 2 weeks post-reactivation, whereas direct activation of cannabinoid receptors did not produce significant effects on morphine-induced CPP. However, boosting endocannabinoid signaling by inhibition of anandamide metabolism promoted a transient CB1-dependent enhancement of the CPP.
在回忆与药物体验相关的记忆后，药物成瘾者会不断地重新寻求药物。人们相信，成功应用阻断记忆再巩固的疗法可能会结束药物成瘾的持续循环。
本研究旨在探讨内源性大麻素系统的调节是否会影响先前与吗啡环境配对的大鼠阿片类相关快感记忆的再巩固。
雄性 Wistar 大鼠接受训练以获得吗啡条件性位置偏好（CPP）。一周后，通过短暂暴露于药物配对环境来重新激活吗啡-CPP 记忆。在记忆再激活后，吗啡训练大鼠的独立组立即接受不同剂量的大麻素 CB1 受体拮抗剂利莫那班、CB2 选择性拮抗剂 AM630、强效 CB1/CB2 激动剂 WIN 55,212-2、脂肪酸酰胺水解酶抑制剂 URB597 或载体的单次皮下注射。在再激活后 1 周和 2 周时测试吗啡-CPP。
阻断 CB1（而非 CB2）大麻素受体在再激活后 1 周和 2 周的测试中均损害了吗啡-CPP 的再巩固，而直接激活大麻素受体对吗啡诱导的 CPP 没有显著影响。然而，通过抑制花生四烯酸代谢来增强内源性大麻素信号传导，促进了 CPP 的短暂的 CB1 依赖性增强。
