PMID- 25981172
OWN - NLM
STAT- MEDLINE
DCOM- 20170504
LR  - 20220316
IS  - 1873-2402 (Electronic)
IS  - 0006-3223 (Linking)
VI  - 79
IP  - 10
DP  - 2016 May 15
TI  - Anxiety, Stress, and Fear Response in Mice With Reduced Endocannabinoid Levels.
PG  - 858-868
LID - S0006-3223(15)00314-5 [pii]
LID - 10.1016/j.biopsych.2015.03.033 [doi]
AB  - BACKGROUND: Disruption of the endocannabinoid system through pharmacological or 
      genetic invalidation of cannabinoid CB1 receptors has been linked to depression 
      in humans and depression-like behaviors in mice. The two main endogenous 
      cannabinoids, anandamide and 2-arachidonoyl glycerol (2-AG), are produced on 
      demand from phospholipids. The pathways and enzymes involved in endocannabinoid 
      biosynthesis thus play a major role in regulating the activity of this system. 
      This study investigates the role of the main 2-AG producing enzyme diacylglycerol 
      lipase alpha (DAGL-alpha). METHODS: We generated and used knockout mice lacking DAGL-alpha 
      (Dagla(-/-)) to assess the behavioral consequences of reduced endocannabinoid 
      levels in the brain. We performed different behavior tests to determine anxiety- 
      and depression-related behavioral changes in Dagla(-/-) mice. We also analyzed 
      expression of genes related to the endocannabinoid system via real-time 
      polymerase chain reaction and used the mitotic marker 5-bromo-2'-deoxyuridine to 
      analyze adult neurogenesis. RESULTS: Dagla(-/-) animals show an 80% reduction of 
      brain 2-AG levels but also a reduction in cortical and amygdalar anandamide. The 
      behavioral changes induced by Dagla deletion include a reduced exploration of the 
      central area of the open field, a maternal neglect behavior, a fear extinction 
      deficit, increased behavioral despair, increased anxiety-related behaviors in the 
      light/dark box, and reduced hippocampal neurogenesis. Some of these behavioral 
      changes resemble those observed in animals lacking the CB1 receptor. CONCLUSIONS: 
      Our findings demonstrate that the deletion of Dagla adversely affects the 
      emotional state of animals and results in enhanced anxiety, stress, and fear 
      responses.
CI  - Copyright (c) 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All 
      rights reserved.
FAU - Jenniches, Imke
AU  - Jenniches I
AD  - Institute of Molecular Psychiatry, University of Bonn, Bonn, Germany.; Institute 
      of Physiological Chemistry, University Medical Center of the Johannes Gutenberg 
      University Mainz, Mainz, Germany.
FAU - Ternes, Svenja
AU  - Ternes S
AD  - Institute of Molecular Psychiatry, University of Bonn, Bonn, Germany.; Institute 
      of Physiological Chemistry, University Medical Center of the Johannes Gutenberg 
      University Mainz, Mainz, Germany.
FAU - Albayram, Onder
AU  - Albayram O
AD  - Institute of Molecular Psychiatry, University of Bonn, Bonn, Germany.; Institute 
      of Physiological Chemistry, University Medical Center of the Johannes Gutenberg 
      University Mainz, Mainz, Germany.
FAU - Otte, David M
AU  - Otte DM
AD  - Institute of Molecular Psychiatry, University of Bonn, Bonn, Germany.; Institute 
      of Physiological Chemistry, University Medical Center of the Johannes Gutenberg 
      University Mainz, Mainz, Germany.
FAU - Bach, Karsten
AU  - Bach K
AD  - Institute of Molecular Psychiatry, University of Bonn, Bonn, Germany.; Institute 
      of Physiological Chemistry, University Medical Center of the Johannes Gutenberg 
      University Mainz, Mainz, Germany.
FAU - Bindila, Laura
AU  - Bindila L
AD  - Institute of Physiological Chemistry, University Medical Center of the Johannes 
      Gutenberg University Mainz, Mainz, Germany.
FAU - Michel, Kerstin
AU  - Michel K
AD  - Institute of Molecular Psychiatry, University of Bonn, Bonn, Germany.; Institute 
      of Physiological Chemistry, University Medical Center of the Johannes Gutenberg 
      University Mainz, Mainz, Germany.
FAU - Lutz, Beat
AU  - Lutz B
AD  - Institute of Physiological Chemistry, University Medical Center of the Johannes 
      Gutenberg University Mainz, Mainz, Germany.
FAU - Bilkei-Gorzo, Andras
AU  - Bilkei-Gorzo A
AD  - Institute of Physiological Chemistry, University Medical Center of the Johannes 
      Gutenberg University Mainz, Mainz, Germany.
FAU - Zimmer, Andreas
AU  - Zimmer A
AD  - Institute of Physiological Chemistry, University Medical Center of the Johannes 
      Gutenberg University Mainz, Mainz, Germany.. Electronic address: 
      a.zimmer@uni-bonn.de.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150414
PL  - United States
TA  - Biol Psychiatry
JT  - Biological psychiatry
JID - 0213264
RN  - 0 (Endocannabinoids)
RN  - EC 3.1.1.34 (Lipoprotein Lipase)
SB  - IM
CIN - Biol Psychiatry. 2016 May 15;79(10 ):e78-e79. PMID: 26212898
CIN - Biol Psychiatry. 2016 May 15;79(10 ):e80-e81. PMID: 26410564
CIN - Biol Psychiatry. 2016 May 15;79(10 ):792-793. PMID: 27130852
MH  - Animals
MH  - Anxiety/*metabolism
MH  - Brain/metabolism
MH  - Cohort Studies
MH  - Endocannabinoids/*metabolism
MH  - Exploratory Behavior/physiology
MH  - Extinction, Psychological/physiology
MH  - Fear/*physiology
MH  - Female
MH  - Lipoprotein Lipase/*deficiency/genetics
MH  - Male
MH  - Maternal Behavior/physiology
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Motor Activity/physiology
MH  - Neurogenesis/physiology
MH  - Social Behavior
MH  - Stress, Psychological/*metabolism
OTO - NOTNLM
OT  - Anxiety
OT  - Cannabinoids
OT  - Dagla
OT  - Depression
OT  - Fear extinction
OT  - Stress
EDAT- 2015/05/20 06:00
MHDA- 2017/05/05 06:00
CRDT- 2015/05/19 06:00
PHST- 2014/10/23 00:00 [received]
PHST- 2015/03/20 00:00 [revised]
PHST- 2015/03/27 00:00 [accepted]
PHST- 2015/05/19 06:00 [entrez]
PHST- 2015/05/20 06:00 [pubmed]
PHST- 2017/05/05 06:00 [medline]
AID - S0006-3223(15)00314-5 [pii]
AID - 10.1016/j.biopsych.2015.03.033 [doi]
PST - ppublish
SO  - Biol Psychiatry. 2016 May 15;79(10):858-868. doi: 10.1016/j.biopsych.2015.03.033. 
      Epub 2015 Apr 14.