Department of Neurology, McGill University, Montreal, QC, Canada.
Neuropsychopharmacology. 2011 Nov;36(12):2469-76. doi: 10.1038/npp.2011.135. Epub 2011 Jul 20.
The neurobiology of tobacco use is poorly understood, possibly in part because the relevant mechanisms might differ depending on past nicotine exposure and degree of addiction. In the present study we investigated whether these factors might affect the role of dopamine (DA). Using the acute phenylalanine/tyrosine depletion method (APTD), DA synthesis was transiently decreased in three groups of abstinent smokers (n=47): (1) early low-frequency smokers, who had smoked a maximum of five cigarettes per day for less than one year, (2) stable low-frequency smokers smoking at the same level as early low-frequency smokers for at least 3 years, and (3) stable high-frequency smokers, who smoked a minimum of 10 or more cigarettes per day for at least 5 years. Motivation to obtain tobacco was measured using a progressive ratio breakpoint schedule for nicotine-containing and de-nicotinized cigarettes. Compared with a nutritionally balanced control mixture, APTD decreased the self-administration of nicotine-containing cigarettes, and this occurred in all three groups of smokers. The results suggest that DA influenced the willingness to sustain effort for nicotine reward, and this was seen in participants at all three levels of cigarette addiction. In the transition from sporadic to addicted use, the role of DA in the motivation to seek drug may change less than previously proposed.
烟草使用的神经生物学机制了解甚少，部分原因可能是相关机制可能因过去的尼古丁暴露和成瘾程度而异。在本研究中，我们研究了这些因素是否会影响多巴胺（DA）的作用。使用急性苯丙氨酸/酪氨酸耗竭法（APTD），三组戒断吸烟者（n=47）的 DA 合成短暂下降：（1）早期低频吸烟者，每天吸烟最多 5 支，持续时间不到一年，（2）稳定低频吸烟者，每天吸烟量与早期低频吸烟者相同，持续时间至少 3 年，（3）稳定高频吸烟者，每天至少吸烟 10 支或更多，持续时间至少 5 年。使用含有尼古丁和不含尼古丁的香烟递增比例断点时间表来衡量获得烟草的动机。与营养平衡的对照混合物相比，APTD 降低了含有尼古丁的香烟的自我给药，而且这种情况发生在所有三组吸烟者中。结果表明，DA 影响了维持尼古丁奖励的努力意愿，这在所有三个吸烟成瘾水平的参与者中都有体现。在从偶尔吸烟到成瘾使用的转变过程中，DA 在寻求药物动机中的作用变化可能比之前提出的要小。
