Cannabinoid CB1 antagonist SR 141716A attenuates reinstatement of heroin self-administration in heroin-abstinent rats
Cannabinoid CB1 antagonist SR 141716A attenuates reinstatement of heroin self-administration in heroin-abstinent rats
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DOI：
10.1016/j.neuropharm.2005.01.022
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发表时间：
2005-06-01
影响因子：
4.7
通讯作者：
Fratta, W
中科院分区：
文献类型：
--
作者：
Fattore, L;Spano, S;Fratta, W
对有海洛因自我给药史的大鼠进行了研究，以评估在恢复海洛因寻求行为的动物模型中大麻素和阿片类药物之间发生的相互作用。训练大鼠自我给予海洛因，并在长期消退后用以下非偶然的非强化药物之一致敏：生理盐水（或溶媒）、海洛因、合成大麻素CB 1受体激动剂（WIN 55，212 -2或CP 55，940）、阿片拮抗剂（纳洛酮）或CB 1拮抗剂（SR 141716 A），单独或联合给药。在引发后，记录下按压活动，并将其与先前训练和消退阶段期间观察到的活动进行比较。本研究的结果表明，（一）引发注射海洛因，（0.1 mg/kg）以及CB 1激动剂WIN 55，212 -2（0.15或0.30毫克/千克）和粗蛋白55，940（0.05或0.1毫克/公斤）完全恢复海洛因寻求行为;（ii）纳洛酮（1 mg/kg）和SR 141716 A的引发（0.3 mg/kg）单独给药时无影响;（iii）用纳洛酮或SR 141716 A预处理可完全预防海洛因诱导的复发;（iv）用SR 141716 A预处理显著降低了WIN 55，212 -2和CP 55，940引发效应。这些结果表明，大麻素CB 1受体发挥重要作用的机制，潜在的复发海洛因寻求和描绘CB 1拮抗剂作为可能的治疗药物用于预防复发海洛因滥用。(c)2005爱思唯尔有限公司保留所有权利。
Rats with a previous history of heroin self-administration were studied to assess interactions occurring between cannabinoids and opioids in an animal model of reinstatement of heroin-seeking behaviour. Rats were trained to self-administer heroin and after a long-term extinction were primed with one of the following non-contingent non-reinforced drug administrations: saline (or vehicle), heroin, synthetic cannabinoid CB1 receptor agonists (WIN 55,212-2 or CP 55,940), opioid antagonist (naloxone) or CB1 antagonist (SR 141716A), alone or in combination. After primings, lever-pressing activity was recorded and compared to those observed during previous phases of training and extinction. Results of this study showed that (i) priming injections of heroin (0.1 mg/kg) as well as CB1 agonists WIN 55,212-2 (0.15 or 0.30 mg/kg) and CP 55,940 (0.05 or 0.1 mg/kg) completely restore heroin-seeking behaviour; (ii) primings of naloxone (1 mg/kg) and SR 141716A (0.3 mg/kg) had no effect when administered alone; (iii) heroin-induced reinstatement was fully prevented by pre-treatment with either naloxone or SR 141716A; (iv) pre-treatment with SR 141716A significantly reduced WIN 55,212-2 and CP 55,940 priming effects. These results suggest that cannabinoid CB1 receptors play an important role in the mechanisms underlying relapse to heroin-seeking and depict CB1 antagonists as possible therapeutic agents for use in the prevention of relapse to heroin abuse. (c) 2005 Elsevier Ltd. All rights reserved.