PMID- 29842858
OWN - NLM
STAT- MEDLINE
DCOM- 20190213
LR  - 20211204
IS  - 1873-7064 (Electronic)
IS  - 0028-3908 (Linking)
VI  - 138
DP  - 2018 Aug
TI  - Pharmacological inhibition of 2-arachidonoilglycerol hydrolysis enhances memory 
      consolidation in rats through CB2 receptor activation and mTOR signaling 
      modulation.
PG  - 210-218
LID - S0028-3908(18)30265-X [pii]
LID - 10.1016/j.neuropharm.2018.05.030 [doi]
AB  - The endocannabinoid system is a key modulator of memory consolidation for 
      aversive experiences. We recently found that the fatty acid amide hydrolase 
      (FAAH) inhibitor URB597, which increases anandamide levels by inhibiting its 
      hydrolysis, facilitates memory consolidation through a concurrent activation of 
      both cannabinoid receptor type 1 (CB1) and 2 (CB2). Here, we investigated the 
      role played on memory consolidation by the other major endocannabinoid, 
      2-arachidonoylglycerol (2-AG). To this aim, we tested the effects of 
      pharmacological inhibition of monoacylglycerol lipase (MAGL) through systemic 
      administration of the MAGL inhibitor JZL184 to rats immediately after training of 
      the inhibitory avoidance task. Pharmacological enhancement of 2-AG tone 
      facilitated memory consolidation through activation of CB2 receptor signaling. 
      Moreover, we found that increased 2-AG signaling prevented the activation of the 
      mammalian target of rapamycin (mTOR) signaling pathway in the hippocampus through 
      a CB2-dependent mechanism. Our results identify a fundamental role for 2-AG and 
      CB2 receptors in the modulation of memory consolidation for aversive experiences.
CI  - Copyright (c) 2018 Elsevier Ltd. All rights reserved.
FAU - Ratano, Patrizia
AU  - Ratano P
AD  - Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, 
      Italy.
FAU - Petrella, Carla
AU  - Petrella C
AD  - Institute of Cell Biology and Neurobiology, CNR, Via del Fosso di Fiorano, 64, 
      00143, Rome, Italy; European Brain Research Institute (EBRI), Rome, Italy.
FAU - Forti, Fabrizio
AU  - Forti F
AD  - Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, 
      Italy.
FAU - Passeri, Pamela Petrocchi
AU  - Passeri PP
AD  - Institute of Cell Biology and Neurobiology, CNR, Via del Fosso di Fiorano, 64, 
      00143, Rome, Italy.
FAU - Morena, Maria
AU  - Morena M
AD  - Hotchkiss Brain Institute, Departments of Cell Biology & Anatomy and Psychiatry, 
      University of Calgary, Calgary, Canada.
FAU - Palmery, Maura
AU  - Palmery M
AD  - Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, 
      Italy.
FAU - Trezza, Viviana
AU  - Trezza V
AD  - Department of Science, Section of Biomedical Sciences and Technologies, 
      University "Roma Tre", Rome, Italy.
FAU - Severini, Cinzia
AU  - Severini C
AD  - Institute of Cell Biology and Neurobiology, CNR, Via del Fosso di Fiorano, 64, 
      00143, Rome, Italy; European Brain Research Institute (EBRI), Rome, Italy.
FAU - Campolongo, Patrizia
AU  - Campolongo P
AD  - Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, 
      Italy; IRCCS Santa Lucia Foundation, 00143 Rome, Italy. Electronic address: 
      patrizia.campolongo@uniroma1.it.
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20180526
PL  - England
TA  - Neuropharmacology
JT  - Neuropharmacology
JID - 0236217
RN  - 0 (Arachidonic Acids)
RN  - 0 (Benzodioxoles)
RN  - 0 (Cannabinoid Receptor Modulators)
RN  - 0 (Cnr1 protein, rat)
RN  - 0 (Cnr2 protein, rat)
RN  - 0 (Endocannabinoids)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Glycerides)
RN  - 0 (JZL 184)
RN  - 0 (Nootropic Agents)
RN  - 0 (Piperidines)
RN  - 0 (Receptor, Cannabinoid, CB1)
RN  - 0 (Receptor, Cannabinoid, CB2)
RN  - 8D239QDW64 (glyceryl 2-arachidonate)
RN  - EC 2.7.1.1 (mTOR protein, rat)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.1.1.23 (Monoacylglycerol Lipases)
SB  - IM
MH  - Animals
MH  - Arachidonic Acids/*metabolism
MH  - Avoidance Learning/drug effects/physiology
MH  - Benzodioxoles/pharmacology
MH  - Cannabinoid Receptor Modulators/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Endocannabinoids/*metabolism
MH  - Enzyme Inhibitors/pharmacology
MH  - Glycerides/*metabolism
MH  - Hippocampus/drug effects/metabolism
MH  - Hydrolysis/*drug effects
MH  - Male
MH  - Memory Consolidation/*drug effects/physiology
MH  - Monoacylglycerol Lipases/antagonists & inhibitors/metabolism
MH  - Nootropic Agents/*pharmacology
MH  - Piperidines/pharmacology
MH  - Rats, Sprague-Dawley
MH  - Receptor, Cannabinoid, CB1/metabolism
MH  - Receptor, Cannabinoid, CB2/*metabolism
MH  - Signal Transduction/drug effects
MH  - TOR Serine-Threonine Kinases/*metabolism
OTO - NOTNLM
OT  - Behavior
OT  - CB1 receptor antagonist
OT  - CB2 receptor antagonist
OT  - Fear memory
OT  - Inhibitory avoidance
OT  - JZL184
OT  - JZL184 [4-[Bis(1,3-benzodioxol-5-yl)hydroxymethyl]-1-piperidinecarboxylic acid 
      4-nitrophenyl ester]
OT  - MAGL inhibitor
OT  - Monoacylglycerol lipase (MAGL)
OT  - Rat
OT  - SR141716 
      [5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-N-1-Piperidinyl-1H-pyrazole-3-carboxamide]
OT  - SR144528 [5-(4-chloro-3-methylphenyl)-1- 
      [(4-methylphenyl)methyl]-N-[(1S,2S,4R)-1,3,3-trimethylbicyclo [2.2.1] hept-2-yl] 
      -1H-pyrazole-3-carboxamide]
EDAT- 2018/05/31 06:00
MHDA- 2019/02/14 06:00
CRDT- 2018/05/30 06:00
PHST- 2017/11/07 00:00 [received]
PHST- 2018/04/09 00:00 [revised]
PHST- 2018/05/24 00:00 [accepted]
PHST- 2018/05/31 06:00 [pubmed]
PHST- 2019/02/14 06:00 [medline]
PHST- 2018/05/30 06:00 [entrez]
AID - S0028-3908(18)30265-X [pii]
AID - 10.1016/j.neuropharm.2018.05.030 [doi]
PST - ppublish
SO  - Neuropharmacology. 2018 Aug;138:210-218. doi: 10.1016/j.neuropharm.2018.05.030. 
      Epub 2018 May 26.