PMID- 19648913
OWN - NLM
STAT- MEDLINE
DCOM- 20090923
LR  - 20220225
IS  - 1546-1726 (Electronic)
IS  - 1097-6256 (Linking)
VI  - 12
IP  - 9
DP  - 2009 Sep
TI  - Cannabinoid modulation of hippocampal long-term memory is mediated by mTOR 
      signaling.
PG  - 1152-8
LID - 10.1038/nn.2369 [doi]
AB  - 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.
FAU - Puighermanal, Emma
AU  - Puighermanal E
AD  - Laboratori de Neurofarmacologia, Facultat de Ciencies de la Salut i de la Vida, 
      Universitat Pompeu Fabra, Barcelona, Spain.
FAU - Marsicano, Giovanni
AU  - Marsicano G
FAU - Busquets-Garcia, Arnau
AU  - Busquets-Garcia A
FAU - Lutz, Beat
AU  - Lutz B
FAU - Maldonado, Rafael
AU  - Maldonado R
FAU - Ozaita, Andres
AU  - Ozaita A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090802
PL  - United States
TA  - Nat Neurosci
JT  - Nature neuroscience
JID - 9809671
RN  - 0 (Central Nervous System Agents)
RN  - 0 (Protein Synthesis Inhibitors)
RN  - 0 (Receptor, Cannabinoid, CB1)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - 56-12-2 (gamma-Aminobutyric Acid)
RN  - 6C74YM2NGI (Anisomycin)
RN  - 7J8897W37S (Dronabinol)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
CIN - Nat Neurosci. 2009 Sep;12(9):1081-3. PMID: 19710646
MH  - Animals
MH  - Anisomycin/pharmacology
MH  - Central Nervous System Agents/pharmacology
MH  - Cognition/drug effects/physiology
MH  - Dronabinol
MH  - Glutamic Acid/genetics/metabolism
MH  - Hippocampus/drug effects/*physiology
MH  - Male
MH  - Memory/drug effects/*physiology
MH  - Memory Disorders/chemically induced/drug therapy/physiopathology
MH  - Mice
MH  - Mice, Knockout
MH  - Neurons/drug effects/physiology
MH  - Protein Kinases/metabolism
MH  - Protein Synthesis Inhibitors/pharmacology
MH  - Receptor, Cannabinoid, CB1/genetics/*metabolism
MH  - Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors/metabolism
MH  - Ribosomal Protein S6 Kinases, 70-kDa/genetics/metabolism
MH  - Signal Transduction
MH  - Sirolimus/pharmacology
MH  - TOR Serine-Threonine Kinases
MH  - gamma-Aminobutyric Acid/genetics/metabolism
EDAT- 2009/08/04 09:00
MHDA- 2009/09/24 06:00
CRDT- 2009/08/04 09:00
PHST- 2009/04/02 00:00 [received]
PHST- 2009/06/15 00:00 [accepted]
PHST- 2009/08/04 09:00 [entrez]
PHST- 2009/08/04 09:00 [pubmed]
PHST- 2009/09/24 06:00 [medline]
AID - nn.2369 [pii]
AID - 10.1038/nn.2369 [doi]
PST - ppublish
SO  - Nat Neurosci. 2009 Sep;12(9):1152-8. doi: 10.1038/nn.2369. Epub 2009 Aug 2.