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'.

中文翻译：

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烟碱乙酰胆碱受体对攻击行为的调节：动物模型，人类遗传学和临床研究。

神经精神疾病通常因攻击行为而复杂化。对于某些人来说，现有的行为和心理药物治疗无效或带来严重的副作用，因此有必要开发治疗严重侵略性患者的新方法。烟碱型乙酰胆碱受体（nAChRs）是整个大脑中表达的多种多样的配体门控离子通道家族，可影响与神经精神疾病高度相关的行为，包括注意力，情绪和冲动性。尼古丁和其他靶向nAChRs的药物可以在攻击性，防御性和掠夺性攻击的动物模型以及人体实验室研究中减少攻击性。人类遗传学研究表明，编码α-7nAChR的CHRNA7基因与攻击行为之间存在关联，尽管这些效应是异质的，并且受到遗传背景和环境的强烈影响。在这里，我们回顾了动物，人类遗传和临床研究，这些研究支持尼古丁和nAChR信号传导在攻击行为的调节中的一致作用。我们整合了侵略性神经科学的最新研究成果，讨论了可能与nAChRs的这些作用有关的电路，并确定了在对人类患者进行安全有效翻译之前必须回答的多个关键问题。本文是“尼古丁神经药理学的当代进展”专刊的一部分。和临床研究支持尼古丁和nAChR信号在攻击性行为的调节中起着一致的作用。我们整合了侵略性神经科学的最新研究成果，讨论了可能与nAChRs的这些作用有关的电路，并确定了在对人类患者进行安全有效翻译之前必须回答的多个关键问题。本文是“尼古丁神经药理学的当代进展”专刊的一部分。和临床研究支持尼古丁和nAChR信号在攻击性行为的调节中起着一致的作用。我们整合了侵略性神经科学的最新研究成果，讨论了可能与nAChRs的这些作用有关的电路，并确定了在对人类患者进行安全有效翻译之前必须回答的多个关键问题。本文是“尼古丁神经药理学的当代进展”专刊的一部分。