Cannabinoid modulation of hippocampal long-term memory is mediated by mTOR signaling.
Nat Neurosci. 2009-08-02; 12(9): 1152-1158
DOI: 10.1038/nn.2369
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1. Nat Neurosci. 2009 Sep;12(9):1152-8. doi: 10.1038/nn.2369. Epub 2009 Aug 2.
Cannabinoid modulation of hippocampal long-term memory is mediated by mTOR
signaling.
Puighermanal E(1), Marsicano G, Busquets-Garcia A, Lutz B, Maldonado R, Ozaita A.
Author information:
(1)Laboratori de Neurofarmacologia, Facultat de Ciències de la Salut i de la
Vida, Universitat Pompeu Fabra, Barcelona, Spain.
Comment in
Nat Neurosci. 2009 Sep;12(9):1081-3.
Cognitive impairment is one of the most important negative consequences
associated with cannabis consumption. We found that CB1 cannabinoid receptor
(CB1R) activation transiently modulated the mammalian target of rapamycin
(mTOR)/p70S6K pathway and the protein synthesis machinery in the mouse
hippocampus, which correlated with the amnesic properties of
delta9-tetrahydrocannabinol (THC). In addition, non-amnesic doses of either the
mTOR blocker rapamycin or the protein synthesis inhibitor anisomycin abrogated
the amnesic-like effects of THC, pointing to a mechanism involving new protein
synthesis. Moreover, using pharmacological and genetic tools, we found that THC
long-term memory deficits were mediated by CB1Rs expressed on GABAergic
interneurons through a glutamatergic mechanism, as both the amnesic-like effects
and p70S6K phosphorylation were reduced in GABA-CB1R knockout mice and by NMDA
blockade.
DOI: 10.1038/nn.2369
PMID: 19648913 [Indexed for MEDLINE]