University of Bordeaux, France; Centre National de la Recherche Scientifique (CNRS), unit 5287, Institut des Neurosciences Intégratives et Cognitives d'Aquitaine (INCIA), Bordeaux, France.
University of Bordeaux, France; Institut National pour la Santé et la Recherche Médicale (INSERM), unit 1215, Neurocentre Magendie, Bordeaux, France.
Int J Biochem Cell Biol. 2024 Nov;176:106669. doi: 10.1016/j.biocel.2024.106669. Epub 2024 Sep 25.
The study of the mechanism of action of classical psychedelics has gained significant interest due to their clinical potential in the treatment of several psychiatric conditions, including major depressive and anxiety disorders. These drugs bind 5-hydroxytryptamine receptors (5-HTR) including 5-HTR, 5-HTR, 5-HTR, and/or 5-HTR, as well as other targets. 5-HTRs regulate the activity of ascending monoaminergic neurons, a mechanism primarily involved in the action of classical antidepressant drugs, antipsychotics, and drugs of abuse. Sparse neurochemical data have been produced on the control of monoaminergic neuron activity in response to classical psychedelics. Here we review the available data in order to determine whether classical psychedelics have specific neurochemical effects on serotonergic, dopaminergic, and noradrenergic neurons. The data show that these drugs have disparate effects on each monoaminergic system, demonstrating a complex response with state-dependent and region-specific effects. For instance, several psychedelics inhibit the firing of serotonergic neurons, although this is not necessarily associated with a decrease in serotonin release in all regions. Noradrenergic neuron spontaneous activity also appears to be inhibited by psychedelics, also not necessarily associated with a decrease in noradrenaline release in all regions. Psychedelics influence on dopaminergic systems is also complex as the above-mentioned 5-HTRs may have opposing effects on dopaminergic neuron activity, in a state-dependent manner. There is an apparent lack of clear neuronal signature induced by psychedelics on monoaminergic neuron activity despite specific recurrent mechanisms. This review provides a current summary of the action of psychedelics on monoamine neuromodulators serotonin, dopamine and noradrenaline, compiling reoccurring and contradictory findings demonstrating that a monoamine signature of psychedelics, if applicable, would be state- and region-dependant.
经典迷幻剂作用机制的研究引起了人们的极大兴趣，因为它们在治疗几种精神疾病方面具有临床潜力，包括重度抑郁症和焦虑症。这些药物与 5-羟色胺受体（5-HTR）结合，包括 5-HTR1A、5-HTR2A、5-HTR2C 和/或 5-HTR7，以及其他靶点。5-HTR 调节上行单胺能神经元的活动，这一机制主要涉及经典抗抑郁药、抗精神病药和滥用药物的作用。关于经典迷幻剂对单胺能神经元活性的控制，仅有少量神经化学数据。本文综述了现有数据，以确定经典迷幻剂是否对 5-羟色胺能、多巴胺能和去甲肾上腺素能神经元具有特定的神经化学作用。数据表明，这些药物对每种单胺能系统都有不同的作用，表现出复杂的反应，具有状态依赖性和区域特异性。例如，几种迷幻剂抑制 5-羟色胺能神经元的放电，尽管这并不一定与所有区域 5-羟色胺释放的减少有关。去甲肾上腺素能神经元的自发活动似乎也被迷幻剂抑制，也不一定与所有区域去甲肾上腺素释放的减少有关。迷幻剂对多巴胺能系统的影响也很复杂，因为上述 5-HTR 可能以状态依赖的方式对多巴胺能神经元活动产生相反的影响。尽管存在特定的反复出现的机制，但迷幻剂对单胺能神经元活性的影响似乎缺乏明显的神经元特征。本综述提供了迷幻剂对单胺能神经调质 5-羟色胺、多巴胺和去甲肾上腺素作用的最新总结，总结了反复出现的和矛盾的发现，表明迷幻剂的单胺特征（如果适用）将取决于状态和区域。
