TY  - JOUR
PY  - 2012//
TI  - Acute Cannabinoids Impair Working Memory through Astroglial CB(1) Receptor Modulation of Hippocampal LTD
JO  - Cell
A1  - Han, Jing
A1  - Kesner, Philip
A1  - Metna-Laurent, Mathilde
A1  - Duan, Tingting
A1  - Xu, Lin
A1  - Georges, Francois
A1  - Koehl, Muriel
A1  - Abrous, Djoher Nora
A1  - Mendizabal-Zubiaga, Juan
A1  - Grandes, Pedro
A1  - Liu, Qingsong
A1  - Bai, Guang
A1  - Wang, Weixu
A1  - Xiong, Lize
A1  - Ren, Wei
A1  - Marsicano, Giovanni
A1  - Zhang, Xia
SP  - 1039
EP  - 1050
VL  - 148
IS  - 5
N2  - 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.<p />  <p>Language: en</p>
LA  - en
SN  - 0092-8674
UR  - http://dx.doi.org/10.1016/j.cell.2012.01.037
ID  - ref1
ER  -