A cannabinoid mechanism in relapse to cocaine seeking
A cannabinoid mechanism in relapse to cocaine seeking
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DOI：
10.1038/nm1001-1151
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发表时间：
2001-10-01
期刊：
影响因子：
82.9
通讯作者：
Schoffelmeer, ANM
中科院分区：
文献类型：
--
作者：
De Vries, TJ;Shaham, Y;Schoffelmeer, ANM
即使在长期戒毒后，可卡因成瘾的治疗也受到高复发率的阻碍。再次接触可卡因(1)、再次暴露于以前与可卡因有关的刺激(2)或暴露于压力(3)可触发这种对强制使用可卡因的复发。在实验室大鼠中，类似的事件在长时间戒断后恢复寻找可卡因，从而为研究复吸可卡因的神经机制提供了一个模型。内源性大麻素系统与许多神经精神疾病有关，包括药物成瘾(7，8)。大麻的有效成分Delta9-四氢大麻酚激活中脑边缘多巴胺(DA)奖励系统(9，10)，并在药物滥用的临床前模型中具有奖励作用(8，11，12)。我们在此报告合成大麻素激动剂HU210(参考文献)。13)，会导致在长时间戒断后再次寻求可卡因。此外，选择性CB1受体拮抗剂SR141716A(参考文献)。14)，可减轻因再次暴露于与可卡因相关的线索或可卡因本身而导致的复发，但不能减少因暴露于压力而导致的复发。这些数据揭示了大麻素系统在寻求可卡因复吸的神经元过程中的重要作用，并为使用大麻素受体拮抗剂预防复吸可卡因提供了理论依据。
Treatment of cocaine addiction is hampered by high rates of relapse even after prolonged drug abstinence. This relapse to compulsive cocaine use can be triggered by re-exposure to cocaine(1), by re-exposure to stimuli previously associated with cocaine(2) or by exposure to stress(3). In laboratory rats, similar events reinstate cocaine seeking after prolonged withdrawal periods', thus providing a model to study neuronal mechanisms underlying the relapse to cocaine. The endocannabinoid system has been implicated in a number of neuropsychiatric conditions, including drug addiction(7,8). The active ingredient of marijuana, Delta9-tetrahydrocannabinol, activates the mesolimbic dopamine (DA) reward system(9,10) and has rewarding effects in preclinical models of drug abuse(8,11,12). We report here that the synthetic cannabinoid agonist, HU210 (ref. 13), provokes relapse to cocaine seeking after prolonged withdrawal periods. Furthermore, the selective CB1 receptor antagonist, SR141716A (ref. 14), attenuates relapse induced by re-exposure to cocaine-associated cues or cocaine itself, but not relapse induced by exposure to stress. These data reveal an important role of the cannabinoid system in the neuronal processes underlying relapse to cocaine seeking, and provide a rationale for the use of cannabinoid receptor antagonists for the prevention of relapse to cocaine use.