Cannabinoid modulation of hippocampal long-term memory is mediated by mTOR signaling

Emma Puighermanal, Giovanni Marsicano, Arnau Busquets-Garcia, Beat Lutz, Rafael Maldonado, Andrés Ozaita

Research output: Contribution to journalArticleResearchpeer-review

293 Citations (Scopus)


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. © 2009 Nature America, Inc. All rights reserved.
Original languageEnglish
Pages (from-to)1152-1158
JournalNature Neuroscience
Issue number9
Publication statusPublished - 1 Sep 2009


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