There is no fast-acting treatment strate-gies against Alzheimer's disease(AD),in particular dementia-related wandering.N,N-dimethyltryptamine(DMT)is a natural psychedelic that may have rapid-onset nootropic effects.In this study,5×FAD transgenic mice which recapitulated amyloid neuropathological features of AD received one single injection of 6 or 12 mg·kg-1 DMT and tested at 0.5,1,and 2 h thereafter in Y-maze for spatial memory.5×FAD transgenic mice exhibited pro-nounced decreases in time spent,number entered,and distance travelled in the novel arm of Y-maze.DMT at 12 mg·kg-1 partially or completely reversed the three behavioral indices at multiple time points,up to 2 h post injection.The rapid-onset behavioral improvement was consistent with pharmacokinetic analysis of DMT,showing approximately 30 min to reach the maximum concentra-tion in the brain tissue.The transgenic mice also displayed dramatically impaired hippocampal long-term potentiation(LTP),an electrophysiological feature of memory forma-ti

作者：CHENG Dan；LEI Zhuogui；Benjamin Chun-Kit TONG；Catherine Kin CHIU；LI Ying；King-Ho CHEUNG；ZHANG Zhangjin

来源：中国药理学与毒理学杂志 2023 年 37卷 7期