Article abstract

Nature Neuroscience 12, 1152 - 1158 (2009)
Published online: 2 August 2009 | doi:10.1038/nn.2369

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

Emma Puighermanal1, Giovanni Marsicano2, Arnau Busquets-Garcia1, Beat Lutz3, Rafael Maldonado1 & Andrés Ozaita1

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.

  1. Laboratori de Neurofarmacologia, Facultat de Ciències de la Salut i de la Vida, Universitat Pompeu Fabra, Barcelona, Spain.
  2. INSERM U862, NeuroCentre Magendie Endocannabinoids and Neuroadaptation Group, University of Bordeaux, Bordeaux, France.
  3. Department of Physiological Chemistry, Johannes Gutenberg-University Mainz, Mainz, Germany.

Correspondence to: Andrés Ozaita1 e-mail:


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