PMID- 31654971
OWN - NLM
STAT- MEDLINE
DCOM- 20210324
LR  - 20210324
IS  - 1879-1379 (Electronic)
IS  - 0022-3956 (Print)
IS  - 0022-3956 (Linking)
VI  - 120
DP  - 2020 Jan
TI  - Dual pharmacological inhibitor of endocannabinoid degrading enzymes reduces 
      depressive-like behavior in female rats.
PG  - 103-112
LID - S0022-3956(19)30735-6 [pii]
LID - 10.1016/j.jpsychires.2019.10.010 [doi]
AB  - Major depressive disorder (MDD) is common, often under-treated and a leading 
      cause of disability and mortality worldwide. The causes of MDD remain unclear, 
      including the role of the endocannabinoid system. Intriguingly, the prevalence of 
      depression is significantly greater in women than men. In this study we examined 
      the role of endocannabinoids in depressive behavior. The levels of 
      endocannabinoids, N-arachidonoyl ethanolamide (AEA) and 2-arachidonoyl glycerol 
      (2-AG) were measured along with brain derived neurotrophic factor (BDNF) in 
      postmortem ventral striata of female patients with MDD and non-psychiatric 
      controls, and in Wistar Kyoto (WKY) rat, a selectively inbred strain of rat 
      widely used for testing the depressive behavior. The effect of pharmacological 
      elevation of endocannabinoids through inhibition of their catabolizing enzymes 
      (fatty acid amide hydrolase [FAAH] and monoacyl glycerol lipase [MAGL]) on 
      depressive-like phenotype was also assessed in WKY rat. The findings showed lower 
      levels of endocannabinoids and BDNF in the ventral striata of MDD patients and 
      WKY rats. A dual inhibitor of FAAH and MAGL, JZL195, elevated the 
      endocannabinoids and BDNF levels in ventral striatum, and reduced the 
      depressive-like phenotype in female WKY rats. Collectively, our study suggests a 
      blunted ventral striatal endocannabinoid and BDNF signaling in depressive 
      behavior and concludes that endocannabinoid enhancing agents may have an 
      antidepressant effect.
CI  - Copyright (c) 2019 Elsevier Ltd. All rights reserved.
FAU - Dong, Bin
AU  - Dong B
AD  - Division of Analytical Psychopharmacology, Nathan Kline Institute for Psychiatric 
      Research, Orangeburg, NY, USA.
FAU - Shilpa, Borehalli M
AU  - Shilpa BM
AD  - Division of Analytical Psychopharmacology, Nathan Kline Institute for Psychiatric 
      Research, Orangeburg, NY, USA; School of Basic and Applied Sciences, Dayananda 
      Sagar University, Bangalore, India.
FAU - Shah, Relish
AU  - Shah R
AD  - Division of Analytical Psychopharmacology, Nathan Kline Institute for Psychiatric 
      Research, Orangeburg, NY, USA.
FAU - Goyal, Arjun
AU  - Goyal A
AD  - Division of Analytical Psychopharmacology, Nathan Kline Institute for Psychiatric 
      Research, Orangeburg, NY, USA.
FAU - Xie, Shan
AU  - Xie S
AD  - Division of Analytical Psychopharmacology, Nathan Kline Institute for Psychiatric 
      Research, Orangeburg, NY, USA.
FAU - Bakalian, Mihran J
AU  - Bakalian MJ
AD  - New York State Psychiatric Institute, New York, NY, USA.
FAU - Suckow, Raymond F
AU  - Suckow RF
AD  - Division of Analytical Psychopharmacology, Nathan Kline Institute for Psychiatric 
      Research, Orangeburg, NY, USA; New York State Psychiatric Institute, New York, 
      NY, USA; Department of Psychiatry, Columbia University College of Physicians and 
      Surgeons, New York, NY, USA.
FAU - Cooper, Thomas B
AU  - Cooper TB
AD  - Division of Analytical Psychopharmacology, Nathan Kline Institute for Psychiatric 
      Research, Orangeburg, NY, USA; New York State Psychiatric Institute, New York, 
      NY, USA; Department of Psychiatry, Columbia University College of Physicians and 
      Surgeons, New York, NY, USA.
FAU - Mann, J John
AU  - Mann JJ
AD  - New York State Psychiatric Institute, New York, NY, USA; Department of 
      Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY, 
      USA.
FAU - Arango, Victoria
AU  - Arango V
AD  - New York State Psychiatric Institute, New York, NY, USA; Department of 
      Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY, 
      USA.
FAU - Vinod, K Yaragudri
AU  - Vinod KY
AD  - Division of Analytical Psychopharmacology, Nathan Kline Institute for Psychiatric 
      Research, Orangeburg, NY, USA; Emotional Brain Institute, Orangeburg, NY, USA; 
      Department of Child and Adolescent Psychiatry, New York University School of 
      Medicine, New York, NY, USA. Electronic address: vinod.yaragudri@nki.rfmh.org.
LA  - eng
GR  - R01 MH040210/MH/NIMH NIH HHS/United States
GR  - R03 MH085079/MH/NIMH NIH HHS/United States
GR  - R21 MH106935/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20191011
PL  - England
TA  - J Psychiatr Res
JT  - Journal of psychiatric research
JID - 0376331
RN  - 0 (Bdnf protein, rat)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Carbamates)
RN  - 0 (Endocannabinoids)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (JZL195)
RN  - 0 (Piperazines)
RN  - EC 3.1.1.23 (Monoacylglycerol Lipases)
RN  - EC 3.5.- (Amidohydrolases)
RN  - EC 3.5.1.- (fatty-acid amide hydrolase)
SB  - IM
MH  - Amidohydrolases/*antagonists & inhibitors
MH  - Animals
MH  - *Behavior, Animal/drug effects
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Carbamates/pharmacology
MH  - Depression/*drug therapy/*metabolism
MH  - Disease Models, Animal
MH  - Endocannabinoids/*metabolism
MH  - Enzyme Inhibitors/*pharmacology
MH  - Female
MH  - Monoacylglycerol Lipases/*antagonists & inhibitors
MH  - Piperazines/pharmacology
MH  - Rats
MH  - Rats, Inbred WKY
MH  - Signal Transduction/drug effects
MH  - Ventral Striatum/*metabolism
PMC - PMC6916267
MID - NIHMS1542238
OTO - NOTNLM
OT  - BDNF
OT  - Depressive behavior
OT  - Endocannabinoids
OT  - JZL195
OT  - Ventral striatum
COIS- Conflicts of Interest There are no conflicts of interest to declare other than 
      Dr. Mann who receives royalties for commercial use of the C-SSRS from the 
      Research Foundation for Mental Hygiene. This article was prepared while Dr. 
      Arango was employed at Columbia University and the New York State Psychiatric 
      Institute. The opinions expressed in this article are the author's own and do not 
      reflect the view of the National Institutes of Health, the Department of Health 
      and Human Services, or the United States government
EDAT- 2019/10/28 06:00
MHDA- 2021/03/25 06:00
PMCR- 2021/01/01
CRDT- 2019/10/27 06:00
PHST- 2019/06/26 00:00 [received]
PHST- 2019/09/18 00:00 [revised]
PHST- 2019/10/10 00:00 [accepted]
PHST- 2019/10/28 06:00 [pubmed]
PHST- 2021/03/25 06:00 [medline]
PHST- 2019/10/27 06:00 [entrez]
PHST- 2021/01/01 00:00 [pmc-release]
AID - S0022-3956(19)30735-6 [pii]
AID - 10.1016/j.jpsychires.2019.10.010 [doi]
PST - ppublish
SO  - J Psychiatr Res. 2020 Jan;120:103-112. doi: 10.1016/j.jpsychires.2019.10.010. 
      Epub 2019 Oct 11.