Garcia-Rivas Vernon, Fiancette Jean-François, Cannella Nazzareno, Carbo-Gas Maria, Renault Prisca, Tostain Jessica, Deroche-Gamonet Véronique
Psychobiology of Drug Addiction, NeuroCentre Magendie, INSERM U1215, Bordeaux, France.
University of Bordeaux, Bordeaux, France.
Front Behav Neurosci. 2019 Jul 17;13:159. doi: 10.3389/fnbeh.2019.00159. eCollection 2019.
Nicotine is acknowledged as the key addictive compound of tobacco. Varenicline (Champix or Chantix), mainly acting as a partial agonist at the α4β2 nicotinic receptor, is an approved smoking cessation pharmacotherapy, although with efficacy limited to a portion of smokers. Smokers differ in the motives that drive their drug seeking and Varenicline might be more efficient in some groups more than others. Studies in rodents revealed that nicotine-seeking is strongly supported by complex interactions between nicotine and environmental cues, and notably the ability of nicotine to enhance the reinforcing properties of salient environmental stimuli. It is not yet understood whether the decrease of nicotine-seeking by acute Varenicline in rats results from antagonism of the primary reinforcing effects of nicotine, of the reinforcement-enhancing effect of nicotine on cues, or of a combination of both. Thanks to a protocol that allows assessment of the reinforcement-enhancing effect of nicotine on cues during self-administration in rats, we showed that Varenicline targets both nicotine reinforcing effects and reinforcement-enhancing effect of nicotine on cues. Importantly, individual variations in the latter determined the amplitude of acute Varenicline-induced decrease in seeking. These results suggest that Varenicline might be more beneficial in smokers who are more sensitive to nicotine effects on surrounding stimuli.
尼古丁被公认为烟草中的关键成瘾成分。伐尼克兰（畅沛或 Chantix）主要作为 α4β2 烟碱型受体的部分激动剂，是一种已获批准的戒烟药物疗法，不过其疗效仅局限于一部分吸烟者。吸烟者在驱使他们寻求药物的动机方面存在差异，伐尼克兰在某些群体中可能比在其他群体中更有效。对啮齿动物的研究表明，尼古丁与环境线索之间的复杂相互作用，尤其是尼古丁增强显著环境刺激强化特性的能力，有力地支持了对尼古丁的寻求行为。目前尚不清楚大鼠急性给予伐尼克兰后尼古丁寻求行为的减少，是由于拮抗了尼古丁的主要强化作用、尼古丁对线索的强化增强作用，还是两者的综合作用。借助一项能在大鼠自我给药过程中评估尼古丁对线索强化增强作用的实验方案，我们表明伐尼克兰既能作用于尼古丁的强化作用，也能作用于尼古丁对线索的强化增强作用。重要的是，后者的个体差异决定了急性伐尼克兰诱导的寻求行为减少的幅度。这些结果表明，伐尼克兰可能对那些对尼古丁对周围刺激的影响更为敏感的吸烟者更有益。
