Psilocybin facilitates fear extinction in mice by promoting hippocampal neuroplasticity

作     者：Yingjie Du Yunfeng Li Xiangting Zhao Yishan Yao Bin Wang Liming Zhang Guyan Wang Yingjie Du;Yunfeng Li;Xiangting Zhao;Yishan Yao;Bin Wang;Liming Zhang;Guyan Wang

作者机构：Department of AnesthesiologyBeijing Tongren HospitalCapital Medical UniversityBeijing 100730China Beijing Institute of Pharmacology and ToxicologyState Key Laboratory of Toxicology and Medical CountermeasuresBeijing Key Laboratory of NeuropsychopharmacologyBeijing 100850China Beijing Institute of Basic Medical SciencesBeijing 100850China Key Laboratory of Microecology-Immune Regulatory Network and Related Diseases Basic Medical College of Jiamusi UniversityJiamusiHeilongjiang 154000China 

出 版 物：《Chinese Medical Journal》 (中华医学杂志（英文版）)

年 卷 期：2023年第136卷第24期

页      面：2983-2992页

核心收录：

学科分类：1008[医学-中药学(可授医学、理学学位)] 1006[医学-中西医结合] 100602[医学-中西医结合临床] 10[医学] 

基　　金：supported by grants from the STI2030-Major Projects(Nos.2021ZD0200900 and 2021ZD0202000) National Natural Science Foundation of China(Nos.81773708,82270411 and 81970344) Beijing Hospitals Authority's Ascent Plan(No.DFL20220203) Beijing Hospitals Authority Clinical Medicine Development of Special Funding Support(No.ZYLX202103) 

主　　题：Brain-derived neurotrophic factor Bromodeoxyuridine Depression Doublecortin domain proteins Extinction,psychological Freezing Hippocampus Neuronal plasticity Psilocybin Stress disorders,post-traumatic 

摘      要：Background:Posttraumatic stress disorder(PTSD)and depression are highly *** exerts substantial therapeutic effects on depression by promoting *** extinction is a key process in the mechanism of first-line exposure-based therapies for *** hypothesized that psilocybin would facilitate fear extinction by promoting hippocampal ***:First,we assessed the effects of psilocybin on percentage of freezing time in an auditory cued fear conditioning(FC)and fear extinction paradigm in *** was administered 30 min before extinction *** extinction testing was performed on the first day;fear extinction retrieval and fear renewal were tested on the sixth and seventh days,***,we verified the effect of psilocybin on hippocampal neuroplasticity using Golgi staining for the dendritic complexity and spine density,Western blotting for the protein levels of brain derived neurotrophic factor(BDNF)and mechanistic target of rapamycin(mTOR),and immunofluorescence staining for the numbers of doublecortin(DCX)-and bromodeoxyuridine(BrdU)-positive ***:A single dose of psilocybin(2.5 mg/kg,i.p.)reduced the increase in the percentage of freezing time induced by FC at 24 h,6th day and 7th day after *** terms of structural neuroplasticity,psilocybin rescued the decrease in hippocampal dendritic complexity and spine density induced by FC;in terms of neuroplasticity related proteins,psilocybin rescued the decrease in the protein levels of hippocampal BDNF and mTOR induced by FC;in terms of neurogenesis,psilocybin rescued the decrease in the numbers of DCX-and BrdU-positive cells in the hippocampal dentate gyrus induced by ***:A single dose of psilocybin facilitated rapid and sustained fear extinction;this effect might be partially mediated by the promotion of hippocampal *** study indicates that psilocybin may be a useful adjunct to exposure-based therap