N, N-dimethyltryptamine, a natural psychedelic, rapidly improves spatial memory and hippocampal longterm potentiation: a potential rapid-acting therapy for dementia-associated wandering
作者机构：School of Chinese Medicine the University of HongKong Department of Neuroscience City University of HongKong School of Chinses Medicine and Mr. and Mrs. Ko Chi Ming Centre for Parkinson’s Disease Research HongKong Baptist University Department of Psychology LKS Faculty of Medicine the University of HongKong Department of Chinese Medicine the University of Hong Kong-Shenzhen Hospital
出 版 物：《中国药理学与毒理学杂志》 (Chinese Journal of Pharmacology and Toxicology)
年 卷 期：2023年第37卷第7期
页 面：489-490页
学科分类：1002[医学-临床医学] 100203[医学-老年医学] 10[医学]
摘 要：There is no fast-acting treatment strategies 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-1DMT and tested at 0.5, 1, and 2 h thereafter in Y-maze for spatial memory. 5×FAD transgenic mice exhibited pronounced decreases in time spent, number entered, and distance travelled in the novel arm of Y-maze. DMT at 12 mg · kg-1partially 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 concentration in the brain tissue. The transgenic mice also displayed dramatically impaired hippocampal long-term potentiation(LTP), an electrophysiological feature of memory formation and consolidation. DMT potently enhanced LTP and restored intracellular calcium activity, expression and phosphorylation of calcium/calmodulin-dependent protein kinase Ⅱ(CaMKⅡ) and AMPA-type glutamate receptor1(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 mitochondrial ATP dynamics in in vivo and in vitro *** results suggest that DMT rapidly improve spatial memory and hippocampal LTP by restoring the CaMKⅡ-GluR1 signaling pathway and mitochondrial ATP production. It may be served as a fast-acting nootropic agent for the treatment of AD in particular wandering.
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