First Author | Puighermanal E | Year | 2009 |
Journal | Nat Neurosci | Volume | 12 |
Issue | 9 | Pages | 1152-8 |
PubMed ID | 19648913 | Mgi Jnum | J:153145 |
Mgi Id | MGI:4361067 | Doi | 10.1038/nn.2369 |
Citation | Puighermanal E, et al. (2009) Cannabinoid modulation of hippocampal long-term memory is mediated by mTOR signaling. Nat Neurosci 12(9):1152-8 |
abstractText | 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. |