Translational Addiction Research Laboratory, Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada.
Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada.
Sci Rep. 2020 Mar 5;10(1):4085. doi: 10.1038/s41598-020-60940-4.
Preclinical studies show that the dopamine D3 receptor (D3R) is involved in the reinstatement of drug seeking and motivation for drugs of abuse. A D3R gene variant, Ser9Gly (rs6280) has been linked to nicotine dependence, yet the mechanisms underlying its involvement in nicotine dependence is unclear. This study investigated the relationship between the Ser9Gly variant and measures of both nicotine reinforcement and cue-elicited craving. Phenotypes of smoking behaviors were assessed in genetically grouped (Glycine vs. No Glycine carriers) current smokers (n = 104, ≥ 10 cigarettes per day). Laboratory measures included a forced choice session (to measure reinforcement of nicotine containing vs. denicotinized cigarettes), and a cue-reactivity session (to measure smoking cues vs. neutral cues elicited craving). The forced choice procedure revealed that subjective ratings were significantly higher in response to nicotinized compared to denicotinized cigarettes; however the Ser9Gly variant did not influence this effect. By comparison, smoking cues elicited greater craving over time compared to neutral cues, and Glycine carriers of the Ser9Gly D3R variant seem to experience a significant blunted cue-elicited craving effect. Results support D3R involvement in nicotine cue reactivity. However, more research is needed to reveal how this gene variant modulates various aspects of nicotine dependence.
临床前研究表明，多巴胺 D3 受体（D3R）参与了药物寻求的恢复和对滥用药物的动机。D3R 基因变异 Ser9Gly（rs6280）与尼古丁依赖有关，但该基因变异参与尼古丁依赖的机制尚不清楚。本研究调查了 Ser9Gly 变异与尼古丁强化和线索诱发渴求的测量值之间的关系。在基因分组（甘氨酸与非甘氨酸携带者）的当前吸烟者（n = 104，每天至少 10 支香烟）中评估了吸烟行为表型。实验室测量包括强制选择阶段（以测量含尼古丁与去尼古丁化香烟的强化）和线索反应阶段（以测量吸烟线索与中性线索诱发的渴求）。强制选择程序表明，与去尼古丁化香烟相比，尼古丁化香烟的主观评分明显更高；然而，Ser9Gly 变异并没有影响这种效果。相比之下，吸烟线索比中性线索更能引起时间更长的渴求，而 Ser9Gly D3R 变异的甘氨酸携带者似乎经历了明显减弱的线索诱发渴求效应。结果支持 D3R 参与尼古丁线索反应。然而，需要更多的研究来揭示这种基因变异如何调节尼古丁依赖的各个方面。
