Acute cannabinoids impair working memory through astroglial CB1 receptor modulation of hippocampal LTD.
Cell. 2012-03-01; 148(5): 1039-1050
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1. Cell. 2012 Mar 2;148(5):1039-50. doi: 10.1016/j.cell.2012.01.037.
Acute cannabinoids impair working memory through astroglial CB1 receptor
modulation of hippocampal LTD.
Han J(1), Kesner P, Metna-Laurent M, Duan T, Xu L, Georges F, Koehl M, Abrous DN,
Mendizabal-Zubiaga J, Grandes P, Liu Q, Bai G, Wang W, Xiong L, Ren W, Marsicano
G, Zhang X.
(1)College of Life Sciences and Key Laboratory of Modern Teaching Technology,
Shaanxi Normal University, Xian, China.
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 Â© 2012 Elsevier Inc. All rights reserved.
PMID: 22385967 [Indexed for MEDLINE]