N,N-dimethyltryptamine,a natural psychedelic,rap-idly improves spatial memory and hippocampal long-term potentiation:a potential rapid-acting therapy for dementia-associated wandering
10.3867/j.issn.1000-3002.2023.07.021
- Author:
Dan CHENG
1
;
Zhuogui LEI
;
TONG Chun-Kit BENJAMIN
;
CHIU Kin CATHERINE
;
Ying LI
;
CHEUNG KING-HO
;
Zhangjin ZHANG
Author Information
1. School of Chinese Medicine
- Keywords:
N,N-dimethyltryptamine;
spatial memory;
long-term potentiation;
Alzheimer's disease
- From:
Chinese Journal of Pharmacology and Toxicology
2023;37(7):489-490
- CountryChina
- Language:Chinese
-
Abstract:
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-tion and consolidation.DMT potently enhanced LTP and restored intracellular calcium activity,expression and phosphorylation of calcium/calmodulin-dependent protein kinase Ⅱ(CaMK Ⅱ)and AMPA-type glutamate receptor 1(GluR1),the two key calcium-activated mediators involved in LTP induction.Adenosine triphosphate(ATP)is purinergic signalling molecules that are involved in LTP induction and maintenance.DMT rapidly increased mito-chondrial ATP dynamics in in vivo and in vitro models.These results suggest that DMT rapidly improve spatial memory and hippocampal LTP by restoring the CaMK Ⅱ-GluR1 signaling pathway and mitochondrial ATP produc-tion.It may be served as a fast-acting nootropic agent for the treatment of AD in particular wandering.
