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首页> 外文期刊>Addiction biology >Cannabinoid receptor stimulation increases motivation for nicotine and nicotine seeking
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Cannabinoid receptor stimulation increases motivation for nicotine and nicotine seeking

机译：大麻素受体刺激增加了尼古丁和寻求尼古丁的动机

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The cannabinoid system appears to play a critical facilitative role in mediating the reinforcing effects of nicotine and relapse to nicotine-seeking behaviour in abstinent subjects based on the actions of cannabinoid (CB) receptor antagonists. However, the effects of CB receptor stimulation on nicotine self-administration and reinstatement have not been systematically studied. Here, we studied the effects of WIN 55,212-2, a CB1/2 agonist, on intravenous nicotine self-administration under fixed-ratio (FR) and progressive-ratio (PR) schedules of reinforcement in rats. The effects of WIN 55,212-2 on responding for food under similar schedules were also studied. In addition, the effects of WIN 55,212-2 on nicotine- and cue-induced reinstatement of nicotine seeking were also studied, as well as the effects of WIN 55,212-2 on nicotine discrimination. WIN 55,212-2 decreased nicotine self-administration under the FR schedule. However, co-administration of WIN 55,212-2 with nicotine decreased responding for food, which suggests that this effect was non-selective. In contrast, WIN 55,212-2 increased both nicotine self-administration and responding for food under the PR schedule, produced dose-dependent reinstatement of nicotine seeking, and enhanced the reinstatement effects of nicotine-associated cues. Some of these effects were reversed by the CB1 antagonist rimonabant, but not by the CB2 antagonist AM630. In the drug discrimination tests between saline and 0.4 mg/kg nicotine, WIN 55,212-2 produced no nicotine-like discriminative effects but significantly potentiated discriminative stimulus effects of nicotine at the low dose through a CB1-receptor-dependent mechanism. These findings indicate that cannabinoid CB1-receptor stimulation increases the reinforcing effects of nicotine and precipitates relapse to nicotine-seeking behaviour in abstinent subjects. Thus, modulating CB1-receptor signalling might have therapeutic value for treating nicotine dependence.
机译：基于大麻素（CB）受体拮抗剂的作用，大麻素系统似乎在介导尼古丁的增强作用和戒断受试者的尼古丁寻求行为的复发中起着关键的促进作用。但是，尚未系统研究CB受体刺激对尼古丁自我给药和恢复的影响。在这里，我们研究了CB1 / 2激动剂WIN 55,212-2对大鼠在固定比例（FR）和渐进比例（PR）强化下静脉内尼古丁自我给药的影响。还研究了WIN 55,212-2对类似时间表下食物响应的影响。此外，还研究了WIN 55,212-2对尼古丁和提示诱导的尼古丁恢复的影响，以及WIN 55,212-2对尼古丁辨别的影响。在FR计划下，WIN 55,212-2减少了尼古丁的自我管理。但是，WIN 55,212-2与尼古丁的共同给药减少了对食物的反应，这表明该作用是非选择性的。相比之下，WIN 55,212-2在PR计划下增加了尼古丁的自我管理和对食物的反应，产生了尼古丁寻找的剂量依赖性恢复，并增强了与尼古丁相关的提示的恢复作用。其中一些作用被CB1拮抗剂利莫那班逆转，但未被CB2拮抗剂AM630逆转。在盐水和0.4 mg / kg尼古丁之间的药物鉴别测试中，WIN 55,212-2没有产生尼古丁样的歧视作用，但通过CB1受体依赖性机制，在低剂量时显着增强了尼古丁的歧视性刺激作用。这些发现表明大麻素CB1受体刺激增强了尼古丁的增强作用，并促使戒烟对象中尼古丁寻求行为的复发。因此，调节CB1-受体信号传导可能具有治疗尼古丁依赖性的治疗价值。

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