title: Cannabinoid modulation of hippocampal long-term memory is mediated by mTOR signaling.
abstract: 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.
authors: Laboratori de Neurofarmacologia, Facultat de Ciències de la Salut i de la Vida, Universitat Pompeu Fabra, Barcelona, Spain.
authors: Emma
authors: E
authors: Puighermanal
authors: Giovanni
authors: G
authors: Marsicano
authors: Arnau
authors: A
authors: Busquets-Garcia
authors: Beat
authors: B
authors: Lutz
authors: Rafael
authors: R
authors: Maldonado
authors: Andrés
authors: A
authors: Ozaita
mesh_terms: D000818:Animals; D000841:Anisomycin / Q000494:pharmacology; D002491:Central Nervous System Agents / Q000494:pharmacology; D003071:Cognition / Q000187:drug effects / Q000502:physiology; D013759:Dronabinol; D018698:Glutamic Acid / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D011494:Protein Kinases / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases; D005680:gamma-Aminobutyric Acid / Q000235:genetics / Q000378:metabolism
chemical_list: D002491:Central Nervous System Agents; D011500:Protein Synthesis Inhibitors; D043884:Receptor, Cannabinoid, CB1; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D000841:Anisomycin; D013759:Dronabinol; D011494:Protein Kinases; C546843:mTOR protein, mouse; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus