CB1 receptor antagonists for the treatment of nicotine addiction
CB1 receptor antagonists for the treatment of nicotine addiction
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DOI：
10.1016/j.pbb.2005.01.024
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发表时间：
2005-06-01
影响因子：
3.6
通讯作者：
Griebel, G
中科院分区：
文献类型：
--
作者：
Cohen, C;Kodas, E;Griebel, G
吸烟是发达国家可避免的死亡和疾病的最大原因。它现在被视为一个复杂的生物心理社会问题，需要有效的药物治疗。尼古丁被认为是烟草烟雾中建立和维持烟草依赖的主要化合物。尼古丁的成瘾作用是通过激活中脑边缘系统和在丘脑核中释放多巴胺来介导的。最近，已经报道了尼古丁和内源性大麻素系统之间存在特定的功能相互作用。联合施用阈下剂量的大麻素激动剂和尼古丁产生奖励效应，并且慢性尼古丁治疗增加边缘系统区域中的内源性大麻素水平。CB1受体在这种相互作用中起着关键作用。CB1基因敲除小鼠对尼古丁的激励作用不太敏感，尽管这取决于实验模型。选择性CB1拮抗剂利莫那班（SR141716）可减少大鼠的尼古丁自我给药和条件提示诱导的尼古丁寻求行为。利莫那班似乎通过减弱内源性大麻素系统和中脑边缘多巴胺能神经元通路的过度活化来减少尼古丁成瘾。利莫那班可能被认为是目前尼古丁成瘾替代治疗的潜在替代品，并可能为希望戒烟的吸烟者提供新的希望。(c)2005年爱思唯尔公司All rights reserved.
Tobacco smoking is the largest cause of avoidable death and disease in developed countries. It is now viewed as a complex bio-psychosocial problem for which effective pharmacological treatments are needed. Nicotine is considered to be the primary compound of tobacco smoke that establishes and maintains tobacco dependence. The addictive effect of nicotine is mediated by activation of the mesolimbic system and the release of dopamine in the nucleus accumbens. Recently, the existence of a specific functional interaction between nicotine and the endocannabinoid system has been reported. Co-administration of sub-threshold doses of a cannabinoid agonist and nicotine produces rewarding effects and chronic nicotine treatment increases endocannabinoid levels in limbic regions. The CB1 receptor plays a key role in this interaction. CB1 knockout mice are less sensitive to the motivational effects of nicotine although this depends on the experimental model. The selective CB1 antagonist, rimonabant (SR141716), reduces nicotine self-administration and nicotine-seeking behavior induced by conditioned cues in rats. Rimonabant appears to reduce nicotine addiction by attenuating the hyperactivation of the endocannabinoid system and the mesolimbic dopaminergic neuronal pathway. Rimonabant may be considered as a potential alternative to the current substitutive treatments of nicotine addiction and may offer a new hope for the treatment of smokers who wish to quit. (c) 2005 Elsevier Inc. All rights reserved.