气候变化领域集成服务门户(CCPortal): Harnessing psilocybin: Antidepressant-like behavioral and synaptic actions of psilocybin are independent of 5-HT2R activation in mice

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DOI	10.1073/pnas.2022489118
	Harnessing psilocybin: Antidepressant-like behavioral and synaptic actions of psilocybin are independent of 5-HT2R activation in mice
	Hesselgrave N.; Troppoli T.A.; Wulff A.B.; Cole A.B.; Thompson S.M.
发表日期	2021
ISSN	00278424
卷号	118 期号:17
英文摘要	Depression is a widespread and devastating mental illness and the search for rapid-acting antidepressants remains critical. There is now exciting evidence that the psychedelic compound psilocybin produces not only powerful alterations of consciousness, but also rapid and persistent antidepressant effects. How psilocybin exerts its therapeutic actions is not known, but it is widely presumed that these actions require altered consciousness, which is known to be dependent on serotonin 2A receptor (5-HT2AR) activation. This hypothesis has never been tested, however. We therefore asked whether psilocybin would exert antidepressant-like responses in mice and, if so, whether these responses required 5-HT2AR activation. Using chronically stressed male mice, we observed that a single injection of psilocybin reversed anhedonic responses assessed with the sucrose preference and female urine preference tests. The antianhedonic response to psilocybin was accompanied by a strengthening of excitatory synapses in the hippocampus—a characteristic of traditional and fast-acting antidepressants. Neither behavioral nor electrophysiological responses to psilocybin were prevented by pretreatment with the 5-HT2A/2C antagonist ketanserin, despite positive evidence of ketanserin’s efficacy. We conclude that psilocybin’s mechanism of antidepressant action can be studied in animal models and suggest that altered perception may not be required for its antidepressant effects. We further suggest that a 5-HT2AR–independent restoration of synaptic strength in cortico-mesolimbic reward circuits may contribute to its antidepressant action. The possibility of combining psychedelic compounds and a 5-HT2AR antagonist offers a potential means to increase their acceptance and clinical utility and should be studied in human depression. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Depression; Hallucination; Hallucinogen; Psychedelic; Serotonin
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/179784
作者单位	Department of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201, United States; Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD 21201, United States; Medical Scientist Training Program, University of Maryland School of Medicine, Baltimore, MD 21201, United States; Molecular Medicine Program, University of Maryland School of Medicine, Baltimore, MD 21201, United States; Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD 21201, United States
推荐引用方式 GB/T 7714	Hesselgrave N.,Troppoli T.A.,Wulff A.B.,et al. Harnessing psilocybin: Antidepressant-like behavioral and synaptic actions of psilocybin are independent of 5-HT2R activation in mice[J],2021,118(17).
APA	Hesselgrave N.,Troppoli T.A.,Wulff A.B.,Cole A.B.,&Thompson S.M..(2021).Harnessing psilocybin: Antidepressant-like behavioral and synaptic actions of psilocybin are independent of 5-HT2R activation in mice.Proceedings of the National Academy of Sciences of the United States of America,118(17).
MLA	Hesselgrave N.,et al."Harnessing psilocybin: Antidepressant-like behavioral and synaptic actions of psilocybin are independent of 5-HT2R activation in mice".Proceedings of the National Academy of Sciences of the United States of America 118.17(2021).