Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA; Vanderbilt Kennedy Center, Vanderbilt University Medical Center, Nashville, TN, USA; Center for Cognitive Medicine, Vanderbilt University Medical Center, Nashville, TN, USA; Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN, USA.
Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA.
Neuropharmacology. 2020 May 1;167:107929. doi: 10.1016/j.neuropharm.2019.107929. Epub 2019 Dec 26.
Neuropsychiatric disorders are frequently complicated by aggressive behaviors. For some individuals, existing behavioral and psychopharmacological treatments are ineffective or confer significant side effects, necessitating development of new ways to treat patients with severe aggression. Nicotinic acetylcholine receptors (nAChRs) are a large and diverse family of ligand-gated ion channels expressed throughout the brain that influence behaviors highly relevant for neuropsychiatric disorders, including attention, mood, and impulsivity. Nicotine and other drugs targeting nAChRs can reduce aggression in animal models of offensive, defensive, and predatory aggression, as well as in human laboratory studies. Human genetic studies have suggested a relationship between the CHRNA7 gene encoding the alpha-7 nAChR and aggressive behavior, although these effects are heterogeneous and strongly influenced by genetic background and environment. Here we review animal, human genetic, and clinical studies supporting a consistent role of nicotine and nAChR signaling in modulation of aggressive behaviors. We integrate findings from recent studies of aggression neuroscience, discuss the circuitry that may be involved in these effects of nAChRs, and identify multiple key questions that must be answered prior to safe and effective translation for human patients. This article is part of the special issue on 'Contemporary Advances in Nicotine Neuropharmacology'.
神经精神疾病常伴有攻击性行为。对于一些个体，现有的行为和精神药理学治疗方法无效或带来显著的副作用，因此需要开发新的方法来治疗严重攻击行为的患者。烟碱型乙酰胆碱受体（nAChRs）是一个广泛而多样的配体门控离子通道家族，在整个大脑中表达，影响与神经精神疾病高度相关的行为，包括注意力、情绪和冲动。尼古丁和其他靶向 nAChRs 的药物可以减少攻击性行为动物模型中的攻击、防御和捕食性攻击，以及人类实验室研究。人类遗传研究表明，编码α-7 nAChR 的 CHRNA7 基因与攻击行为之间存在关系，尽管这些影响存在异质性，并且强烈受到遗传背景和环境的影响。在这里，我们综述了支持尼古丁和 nAChR 信号在调节攻击性行为中的一致作用的动物、人类遗传和临床研究。我们整合了最近关于攻击性行为神经科学的研究结果，讨论了可能涉及这些 nAChR 作用的神经回路，并确定了在安全有效地转化为人类患者之前必须回答的多个关键问题。本文是“当代尼古丁神经药理学进展”特刊的一部分。
