Conti A A, Tolomeo S, Baldacchino A, Steele J D
Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
Population and Behavioural Science Division, School of Medicine, University of St Andrews, St. Andrews, United Kingdom.
Front Pharmacol. 2024 Jul 2;15:1426506. doi: 10.3389/fphar.2024.1426506. eCollection 2024.
Tobacco smoking is the leading preventable cause of death, causing more than six million deaths annually worldwide, mainly due to cardiovascular disease and cancer. Many habitual smokers try to stop smoking but only about 7% are successful, despite widespread knowledge of the risks. Development of addiction to a range of substances is associated with progressive blunting of brain reward responses and sensitisation of stress responses, as described by the allostasis theory of addiction. There is pre-clinical evidence from rodents for a dramatic decrease in brain reward function during nicotine withdrawal.
Here we tested the hypothesis that habitual smokers would also exhibit blunted reward function during nicotine withdrawal using a decision-making task and fMRI.
Our findings supported this hypothesis, with midbrain reward-related responses particularly blunted. We also tested the hypothesis that smokers with a longer duration of smoking would have more pronounced abnormalities. Contrary to expectations, we found that a shorter duration of smoking in younger smokers was associated with the most marked abnormalities, with blunted midbrain reward related activation including the dopaminergic ventral tegmental area.
Given the substantial mortality associated with smoking, and the small percent of people who manage to achieve sustained abstinence, further translational studies on nicotine addiction mechanisms are indicated.
吸烟是主要的可预防死因,全球每年导致超过600万人死亡,主要归因于心血管疾病和癌症。许多烟民试图戒烟,但尽管人们普遍知晓吸烟风险,只有约7%的人成功戒烟。如成瘾的稳态适应理论所述,对一系列物质成瘾的发展与大脑奖赏反应的逐渐迟钝以及应激反应的敏感化有关。有来自啮齿动物的临床前证据表明,尼古丁戒断期间大脑奖赏功能会急剧下降。
在此,我们使用决策任务和功能磁共振成像来检验习惯性吸烟者在尼古丁戒断期间也会表现出奖赏功能迟钝的假设。
我们的研究结果支持了这一假设,中脑奖赏相关反应尤其迟钝。我们还检验了吸烟时间较长的吸烟者会有更明显异常的假设。与预期相反,我们发现年轻吸烟者较短的吸烟时间与最明显的异常有关,中脑奖赏相关激活迟钝,包括多巴胺能腹侧被盖区。
鉴于吸烟相关的大量死亡以及成功实现持续戒烟的人群比例较小,有必要进一步开展关于尼古丁成瘾机制的转化研究。