Colla Michael, Scheerer Hanne, Weidt Steffi, Seifritz Erich, Kronenberg Golo
Department of Psychiatry, Psychotherapy and Psychosomatics, Hospital of Psychiatry, University of Zurich, Zurich, Switzerland.
Front Behav Neurosci. 2021 Dec 3;15:759466. doi: 10.3389/fnbeh.2021.759466. eCollection 2021.
The serendipitous discovery of ketamine's antidepressant effects represents one of the major landmarks in neuropsychopharmacological research of the last 50 years. Ketamine provides an exciting challenge to traditional concepts of antidepressant drug therapy, producing rapid antidepressant effects seemingly without targeting monoaminergic pathways in the conventional way. In consequence, the advent of ketamine has spawned a plethora of neurobiological research into its putative mechanisms. Here, we provide a brief overview of current theories of antidepressant drug action including monoaminergic signaling, disinhibition of glutamatergic neurotransmission, neurotrophic and neuroplastic effects, and how these might relate to ketamine. Given that research into ketamine has not yet yielded new therapies beyond ketamine itself, current knowledge gaps and limitations of available studies are also discussed.
氯胺酮抗抑郁作用的意外发现是过去50年神经精神药理学研究的主要里程碑之一。氯胺酮对传统抗抑郁药物治疗概念提出了令人兴奋的挑战，它似乎不以传统方式作用于单胺能通路，却能产生快速的抗抑郁效果。因此，氯胺酮的出现引发了大量关于其假定机制的神经生物学研究。在此，我们简要概述当前抗抑郁药物作用的理论，包括单胺能信号传导、谷氨酸能神经传递的去抑制、神经营养和神经可塑性效应，以及这些效应与氯胺酮的关系。鉴于对氯胺酮的研究尚未产生除氯胺酮本身之外的新疗法，本文还讨论了现有研究的知识空白和局限性。
