There is growing preclinical evidence for the involvement of glutamate in the behavioral actions of nicotine. The aim of this study, was to investigate the role of N-methyl-D-aspartate (NMDA) receptors in the cognitive and subjective effects of smoking in humans. Sixty regular smokers took part in this double-blind placebo controlled study, that investigated the effect of the NMDA-antagonist memantine (40 mg) and the nicotinic-receptor antagonist mecamylamine (10 mg) on smoking-induced improvement in performance of a task of sustained attention and on smoking-induced changes in subjective effects and craving. Increases in subjective ratings of 'buzzed' following smoking were reversed by memantine, but not by mecamylamine. In contrast, improvement on a Rapid Visual Information Processing task by smoking was opposed by mecamylamine, but not by memantine. Smoking reduced craving for cigarettes, but neither drug altered this effect. Our results suggest that glutamatergic mechanisms may have differential involvement in the subjective and cognitive actions of smoking. Further investigations using different ligands are warranted to fully characterize the role of glutamate underlying the consequences of smoking behavior.

译文

越来越多的临床前证据表明谷氨酸参与尼古丁的行为行为。这项研究的目的是研究N-甲基-D-天冬氨酸 (NMDA) 受体在人类吸烟的认知和主观影响中的作用。60名普通吸烟者参加了这项双盲安慰剂对照研究,研究了NMDA拮抗剂美金刚 (40 mg) 和烟碱受体拮抗剂美加明胺 (10 mg) 对吸烟引起的持续关注任务性能的改善以及吸烟引起的主观影响和渴望变化的影响。美金刚逆转了吸烟后 “嗡嗡声” 的主观评分的增加,但美加明胺却没有。相反,美加明胺反对吸烟对快速视觉信息处理任务的改善,但美金刚反对。吸烟减少了对香烟的渴望,但两种药物都没有改变这种效果。我们的结果表明,谷氨酸能机制可能对吸烟的主观和认知作用有不同的参与。需要使用不同配体进行进一步研究,以充分表征谷氨酸在吸烟行为后果中的作用。

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