Bruijnzeel Adriaan W
Department of Psychiatry, University of Florida, 1149 Newell Dr., Gainesville, FL, 32611, USA.
Department of Neuroscience, University of Florida, Gainesville, FL, USA.
Psychopharmacology (Berl). 2017 May;234(9-10):1419-1437. doi: 10.1007/s00213-016-4513-5. Epub 2016 Dec 28.
The mildly euphoric and cognitive enhancing effects of nicotine play a role in the initiation of smoking, while dysphoria and anxiety associated with smoking cessation contribute to relapse. After the acute withdrawal phase, smoking cues, a few cigarettes (i.e., lapse), and stressors can cause relapse. Human and animal studies have shown that neuropeptides play a critical role in nicotine addiction.
The goal of this paper is to describe the role of neuropeptide systems in the initiation of nicotine intake, nicotine withdrawal, and the reinstatement of extinguished nicotine seeking.
The reviewed studies indicate that several drugs that target neuropeptide systems diminish the rewarding effects of nicotine by preventing the activation of dopaminergic systems. Other peptide-based drugs diminish the hyperactivity of brain stress systems and diminish withdrawal-associated symptom severity. Blockade of hypocretin-1 and nociceptin receptors and stimulation of galanin and neurotensin receptors diminishes the rewarding effects of nicotine. Both corticotropin-releasing factor type 1 and kappa-opioid receptor antagonists diminish dysphoria and anxiety-like behavior associated with nicotine withdrawal and inhibit stress-induced reinstatement of nicotine seeking. Furthermore, blockade of vasopressin 1b receptors diminishes dysphoria during nicotine withdrawal, and melanocortin 4 receptor blockade prevents stress-induced reinstatement of nicotine seeking. The role of neuropeptide systems in nicotine-primed and cue-induced reinstatement is largely unexplored, but there is evidence for a role of hypocretin-1 receptors in cue-induced reinstatement of nicotine seeking.
Drugs that target neuropeptide systems might decrease the euphoric effects of smoking and improve relapse rates by diminishing withdrawal symptoms and improving stress resilience.
尼古丁带来的轻微欣快感和认知增强作用在吸烟起始过程中起作用，而戒烟相关的烦躁不安和焦虑则导致复吸。在急性戒断期过后，吸烟线索、少量香烟（即复吸）和应激源可导致复吸。人类和动物研究表明，神经肽在尼古丁成瘾中起关键作用。
本文的目的是描述神经肽系统在尼古丁摄入起始、尼古丁戒断以及消退的尼古丁寻求行为恢复中的作用。
综述研究表明，几种作用于神经肽系统的药物通过阻止多巴胺能系统的激活来减弱尼古丁的奖赏效应。其他基于肽的药物可减轻脑应激系统的多动，并减轻与戒断相关的症状严重程度。阻断食欲素-1和孤啡肽受体以及刺激甘丙肽和神经降压素受体可减弱尼古丁的奖赏效应。促肾上腺皮质激素释放因子1型和κ-阿片受体拮抗剂均可减轻与尼古丁戒断相关的烦躁不安和焦虑样行为，并抑制应激诱导的尼古丁寻求行为恢复。此外，阻断血管加压素1b受体可减轻尼古丁戒断期间的烦躁不安，而黑皮质素4受体阻断可防止应激诱导的尼古丁寻求行为恢复。神经肽系统在尼古丁激发和线索诱导的恢复中的作用在很大程度上尚未得到探索，但有证据表明食欲素-1受体在线索诱导的尼古丁寻求行为恢复中起作用。
作用于神经肽系统的药物可能会降低吸烟带来的欣快感，并通过减轻戒断症状和提高应激恢复能力来提高戒烟成功率。
