6533b7cffe1ef96bd1258f5b
RESEARCH PRODUCT
Cannabinoid modulation of hippocampal long-term memory is mediated by mTOR signaling.
Andrés OzaitaRafael MaldonadoEmma PuighermanalBeat LutzArnau Busquets-garciaGiovanni Marsicanosubject
MaleCannabinoid receptormedicine.medical_treatmentGlutamic AcidHippocampusReceptors N-Methyl-D-AspartateGlutamatergicchemistry.chemical_compoundMiceCognitionReceptor Cannabinoid CB1Memorymental disordersmedicineAnimalsDronabinolPI3K/AKT/mTOR pathwayAnisomycingamma-Aminobutyric AcidMice KnockoutNeuronsProtein Synthesis InhibitorsSirolimusMemory DisordersChemistryGeneral NeuroscienceTOR Serine-Threonine KinasesRibosomal Protein S6 Kinases 70-kDanervous systemKnockout mouseNMDA receptorPhosphorylationCannabinoidNeuroscienceProtein KinasesAnisomycinCentral Nervous System AgentsSignal Transductiondescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2009-08-02 | Nature neuroscience |