Role of the cannabinoid system in the effects induced by nicotine on anxiety-like behaviour in mice
Role of the cannabinoid system in the effects induced by nicotine on anxiety-like behaviour in mice
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DOI：
10.1007/s00213-005-0251-9
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发表时间：
2006-02-01
影响因子：
3.4
通讯作者：
Maldonado, R
中科院分区：
文献类型：
--
作者：
Balerio, GN;Aso, E;Maldonado, R
原理：尼古丁引起的急性行为效应和动机反应可由内源性大麻素系统调节，支持这两个系统之间存在生理相互作用。目的：本研究旨在探讨大麻素系统在尼古丁诱导的小鼠焦虑和焦虑样反应中的可能参与。方法：动物只暴露一次尼古丁。急性给药低（0.05）或高（0.8 mg/kg, s.c）剂量的尼古丁在升高的正迷宫中产生相反的作用，即焦虑样反应和焦虑样反应。研究了CB1大麻素受体拮抗剂利莫那班（0.25、0.5和1 mg/kg， i.p）和大麻素激动剂Delta 9-四氢大麻酚（Delta 9-THC, 0.1 mg/kg, i.p）预处理对尼古丁诱导的焦虑样和焦虑样反应的影响。结果：利莫那班完全消除了尼古丁诱导的类焦虑作用，增加了尼古丁的类焦虑反应，表明CB1受体参与了这些行为反应。另一方面，Delta 9-THC不能改变尼古丁的焦虑样反应，但会减弱其焦虑样作用。此外，非有效剂量的δ 9-四氢大麻酚和尼古丁的关联产生了明显的抗焦虑样反应。结论：这些结果表明内源性大麻素系统参与了小鼠尼古丁焦虑样行为的调节，为大麻素拮抗剂治疗烟草成瘾提供了新的发现。
Rationale: Acute behavioural effects and motivational responses induced by nicotine can be modulated by the endocannabinoid system supporting the existence of a physiological interaction between these two systems. Objectives: The present study was designed to examine the possible involvement of the cannabinoid system in the anxiolytic- and anxiogenic-like responses induced by nicotine in mice. Methods: Animals were only exposed once to nicotine. The acute administration of low (0.05) or high (0.8 mg/kg, s.c.) doses of nicotine produced opposite effects in the elevated plus-maze, i.e. anxiolytic- and anxiogenic-like responses, respectively. The effects of the pretreatment with the CB1 cannabinoid receptor antagonist, rimonabant (0.25, 0.5 and 1 mg/kg, i.p.), and the cannabinoid agonist, Delta 9-tetrahydrocannabinol (Delta 9-THC, 0.1 mg/kg, ip), were evaluated on the anxiolytic- and anxiogenic-like responses induced by nicotine. Results: Rimonabant completely abolished nicotine-induced anxiolytic-like effects and increased the anxiogenic-like responses of nicotine, suggesting an involvement of CB1 receptors in these behavioural responses. On the other hand, Delta 9-THC failed to modify nicotine anxiolytic-like responses but attenuated its anxiogenic-like effects. In addition, the association of non-effective doses of Delta 9-THC and nicotine produced clear anxiolytic-like responses. Conclusions: These results demonstrate that the endogenous cannabinoid system is involved in the regulation of nicotine anxiety-like behaviour in mice and provide new findings to support the use of cannabinoid antagonists in the treatment of tobacco addiction.