Endocannabinoids underlie reconsolidation of hedonic memories in Wistar rats
Endocannabinoids underlie reconsolidation of hedonic memories in Wistar rats
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DOI：
10.1007/s00213-013-3331-2
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发表时间：
2014-04-01
影响因子：
3.4
通讯作者：
Takahashi, Reinaldo Naoto
中科院分区：
文献类型：
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作者：
De Carvalho, Cristiane Ribeiro;Pamplona, Fabricio Alano;Takahashi, Reinaldo Naoto
吸毒者在回忆与吸毒经历有关的记忆后，不断地故态复萌地寻求毒品。成功地应用阻断记忆再巩固的疗法可能会结束药物复发的连续循环。本研究的目的是探讨内源性大麻素系统的调节是否会影响先前与吗啡配对的大鼠与阿片相关的享乐记忆的再巩固。一周后，在与药物配对的环境中短暂暴露，吗啡-CPP记忆被重新激活。记忆恢复训练结束后，立即皮下注射不同剂量的大麻素CB1受体拮抗剂利莫那班、CB2选择性拮抗剂AM630、CB1/CB2激动剂Win 55、212-2、脂肪酸酰胺水解酶抑制剂URB597或赋形剂。阻断CB1(而不是CB2)大麻素受体可抑制再激活后1周和2周吗啡-CPP的再巩固，而直接激活大麻素受体对吗啡诱导的CPP无明显影响。然而，通过抑制花生胺代谢来增强内源性大麻素信号，促进了CPP的一过性CB1依赖的增强。
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.