title: Acute cannabinoids impair working memory through astroglial CB1 receptor modulation of hippocampal LTD.
abstract: Impairment of working memory is one of the most important deleterious effects of marijuana intoxication in humans, but its underlying mechanisms are presently unknown. Here, we demonstrate that the impairment of spatial working memory (SWM) and in vivo long-term depression (LTD) of synaptic strength at hippocampal CA3-CA1 synapses, induced by an acute exposure of exogenous cannabinoids, is fully abolished in conditional mutant mice lacking type-1 cannabinoid receptors (CB(1)R) in brain astroglial cells but is conserved in mice lacking CB(1)R in glutamatergic or GABAergic neurons. Blockade of neuronal glutamate N-methyl-D-aspartate receptors (NMDAR) and of synaptic trafficking of glutamate α-amino-3-hydroxy-5-methyl-isoxazole propionic acid receptors (AMPAR) also abolishes cannabinoid effects on SWM and LTD induction and expression. We conclude that the impairment of working memory by marijuana and cannabinoids is due to the activation of astroglial CB(1)R and is associated with astroglia-dependent hippocampal LTD in vivo.
authors.affiliation: College of Life Sciences and Key Laboratory of Modern Teaching Technology, Shaanxi Normal University, Xian, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Han
authors.forename: Philip
authors.initials: P
authors.lastname: Kesner
authors.forename: Mathilde
authors.initials: M
authors.lastname: Metna-Laurent
authors.forename: Tingting
authors.initials: T
authors.lastname: Duan
authors.forename: Lin
authors.initials: L
authors.lastname: Xu
authors.forename: Francois
authors.initials: F
authors.lastname: Georges
authors.forename: Muriel
authors.initials: M
authors.lastname: Koehl
authors.forename: Djoher Nora
authors.initials: DN
authors.lastname: Abrous
authors.forename: Juan
authors.initials: J
authors.lastname: Mendizabal-Zubiaga
authors.forename: Pedro
authors.initials: P
authors.lastname: Grandes
authors.forename: Qingsong
authors.initials: Q
authors.lastname: Liu
authors.forename: Guang
authors.initials: G
authors.lastname: Bai
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Lize
authors.initials: L
authors.lastname: Xiong
authors.forename: Wei
authors.initials: W
authors.lastname: Ren
authors.forename: Giovanni
authors.initials: G
authors.lastname: Marsicano
authors.forename: Xia
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D002186:Cannabinoids / Q000494:pharmacology*; D002188:Cannabis / Q000737:chemistry; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D036881:Long-Term Synaptic Depression / Q000187:drug effects; D008570:Memory, Short-Term / Q000187:drug effects*; D051379:Mice; D009473:Neuronal Plasticity; D051381:Rats; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D002186:Cannabinoids; D043884:Receptor, Cannabinoid, CB1