Schmidt Heath D, Rupprecht Laura E, Addy Nii A
Department of Biobehavioral Health Sciences, School of Nursing, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Mol Neuropsychiatry. 2019 Feb;4(4):169-189. doi: 10.1159/000494799. Epub 2018 Nov 19.
Tobacco-related morbidity and mortality continue to be a significant public health concern. Unfortunately, current FDA-approved smoking cessation pharmacotherapies have limited efficacy and are associated with high rates of relapse. Therefore, a better understanding of the neurobiological and neurophysiological mechanisms that promote smoking relapse is needed to develop novel smoking cessation medications. Here, we review preclinical studies focused on identifying the neurotransmitter and neuromodulator systems that mediate nicotine relapse, often modeled in laboratory animals using the reinstatement paradigm, as well as the plasticity-dependent neurophysiological mechanisms that facilitate nicotine reinstatement. Particular emphasis is placed on how these neuroadaptations relate to smoking relapse in humans. We also highlight a number of important gaps in our understanding of the neural mechanisms underlying nicotine reinstatement and critical future directions, which may lead toward the development of novel, target pharmacotherapies for smoking cessation.
与烟草相关的发病率和死亡率仍然是一个重大的公共卫生问题。不幸的是，目前美国食品药品监督管理局（FDA）批准的戒烟药物疗效有限，且复发率很高。因此，需要更好地了解促进吸烟复发的神经生物学和神经生理学机制，以开发新型戒烟药物。在此，我们回顾了临床前研究，这些研究专注于确定介导尼古丁复发的神经递质和神经调质系统，通常在实验室动物中使用恢复模型进行模拟，以及促进尼古丁恢复的可塑性依赖的神经生理机制。特别强调这些神经适应性如何与人类吸烟复发相关。我们还强调了在理解尼古丁恢复背后的神经机制方面存在的一些重要差距以及未来的关键方向，这可能会导向开发用于戒烟的新型靶向药物疗法。
