Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, California.
Campbell Family Mental Health Research Institute, Centre for Addiction & Mental Health (CAMH), Departments of Pharmacology & Toxicology and Psychiatry, University of Toronto, Toronto, Ontario, Canada.
Addict Biol. 2019 Sep;24(5):1087-1095. doi: 10.1111/adb.12679. Epub 2018 Oct 11.
Smoking-induced relief of craving and withdrawal promotes continued cigarette use. Understanding how relief is produced and the role of nicotine in this process may facilitate development of new smoking-cessation therapies. As the US Food and Drug Administration considers setting a standard for reduced nicotine content in cigarettes to improve public health, knowledge of how nicotine contributes to relief also can inform policy. We assessed effects of nicotine using resting state functional magnetic resonance imaging (MRI) and behavioral assessments of craving and negative affect. Twenty-one young (18-25 years old) daily smokers underwent overnight abstinence on 4 days. On each of the following mornings, they self-rated their cigarette craving and negative affect and underwent resting-state functional MRI (fMRI) before and after smoking a cigarette that delivered 0.027, 0.110, 0.231, or 0.763 mg of nicotine. Functional connectivity between the anterior insula and anterior cingulate cortex (ACC) and between the nucleus accumbens and orbitofrontal cortex (OFC) was assessed. Smoking reduced craving, negative affect, and nucleus accumbens-OFC connectivity irrespective of nicotine dose, with positive correlations of the effects on behavioral and connectivity measures. Only the highest nicotine dose (0.763 mg) reduced right anterior insula-ACC connectivity; this reduction was positively correlated with the behavioral effects of the 0.763-mg dose only. While nicotine-based therapies may act on right anterior insula-ACC functional circuits to facilitate smoking cessation, non-nicotine (eg, the conditioned and sensorimotor) aspects of smoking may promote cessation by reducing OFC-accumbens connectivity to alleviate withdrawal.
吸烟引起的渴望和戒断缓解促进了持续吸烟。了解缓解是如何产生的，以及尼古丁在这个过程中的作用，可能有助于开发新的戒烟治疗方法。随着美国食品和药物管理局考虑为改善公众健康设定降低香烟尼古丁含量的标准，了解尼古丁如何缓解也可以为政策提供信息。我们使用静息态功能磁共振成像（MRI）和对渴望和负面情绪的行为评估来评估尼古丁的作用。21 名年轻（18-25 岁）的每日吸烟者在 4 天内进行了一夜的禁欲。在接下来的每个早上，他们自我评估了吸烟的渴望和负面情绪，并在吸烟后进行了静息状态 fMRI（fMRI）评估，吸烟的尼古丁含量分别为 0.027、0.110、0.231 或 0.763mg。评估了前岛叶和前扣带皮层（ACC）之间以及伏隔核和眶额皮层（OFC）之间的功能连接。无论尼古丁剂量如何，吸烟都会降低渴望、负面情绪和伏隔核-OFC 连接，而行为和连接测量的影响呈正相关。只有最高的尼古丁剂量（0.763mg）降低了右侧前岛叶-ACC 连接；这种减少与 0.763mg 剂量的行为影响呈正相关。虽然基于尼古丁的治疗可能作用于右侧前岛叶-ACC 功能回路，以促进戒烟，但吸烟的非尼古丁（例如，条件和感觉运动）方面可能通过降低 OFC-伏隔核连接来减轻戒断，从而促进戒烟。
