| Literature DB >> 22385967 |
Jing Han1, Philip Kesner, Mathilde Metna-Laurent, Tingting Duan, Lin Xu, Francois Georges, Muriel Koehl, Djoher Nora Abrous, Juan Mendizabal-Zubiaga, Pedro Grandes, Qingsong Liu, Guang Bai, Wei Wang, Lize Xiong, Wei Ren, Giovanni Marsicano, Xia Zhang.
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. Copyright ÂEntities:
Mesh：
Substances：
Year: 2012 PMID： 22385967 DOI： 10.1016/j.cell.2012.01.037
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582