PMID- 17684478
OWN - NLM
STAT- MEDLINE
DCOM- 20080701
LR  - 20181201
IS  - 1473-1150 (Electronic)
IS  - 1470-269X (Linking)
VI  - 8
IP  - 3
DP  - 2008 Jun
TI  - Impaired cannabinoid receptor type 1 signaling interferes with stress-coping 
      behavior in mice.
PG  - 196-208
AB  - Dysregulation of the endocannabinoid system is known to interfere with emotional 
      processing of stressful events. Here, we studied the role of cannabinoid receptor 
      type 1 (CB1) signaling in stress-coping behaviors using the forced swim test 
      (FST) with repeated exposures. We compared effects of genetic inactivation with 
      pharmacological blockade of CB1 receptors both in male and female mice. In 
      addition, we investigated potential interactions of the endocannabinoid system 
      with monoaminergic and neurotrophin systems of the brain. Naive CB1 
      receptor-deficient mice (CB1-/-) showed increased passive stress-coping behaviors 
      as compared to wild-type littermates (CB1+/+) in the FST, independent of sex. 
      These findings were partially reproduced in C57BL/6N animals and fully reproduced 
      in female CB1+/+ mice by pharmacological blockade of CB1 receptors with the CB1 
      receptor antagonist SR141716. The specificity of SR141716 was confirmed in female 
      CB1-/- mice, where it failed to affect behavioral performance. Sensitivity to the 
      antidepressants desipramine and paroxetine was preserved, but slightly altered in 
      female CB1-/- mice. There were no genotype differences between CB1+/+ and CB1-/- 
      mice in monoamine oxidase A and B activities under basal conditions, nor in 
      monoamine content of hippocampal tissue after FST exposure. mRNA expression of 
      vesicular glutamate transporter type 1 was unaffected in CB1-/- mice, but mRNA 
      expression of brain-derived neurotrophic factor (BDNF) was reduced in the 
      hippocampus. Our results suggest that impaired CB1 receptor function promotes 
      passive stress-coping behavior, which, at least in part, might relate to 
      alterations in BDNF function.
FAU - Steiner, M A
AU  - Steiner MA
AD  - Max Planck Institute of Psychiatry, Munich, Germany. steiner@mpipsykl.mpg.de
FAU - Wanisch, K
AU  - Wanisch K
FAU - Monory, K
AU  - Monory K
FAU - Marsicano, G
AU  - Marsicano G
FAU - Borroni, E
AU  - Borroni E
FAU - Bachli, H
AU  - Bachli H
FAU - Holsboer, F
AU  - Holsboer F
FAU - Lutz, B
AU  - Lutz B
FAU - Wotjak, C T
AU  - Wotjak CT
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070807
PL  - United States
TA  - Pharmacogenomics J
JT  - The pharmacogenomics journal
JID - 101083949
RN  - 0 (Biogenic Monoamines)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Piperidines)
RN  - 0 (Pyrazoles)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptor, Cannabinoid, CB1)
RN  - 0 (Slc17a7 protein, mouse)
RN  - 0 (Vesicular Glutamate Transport Protein 1)
RN  - EC 1.4.3.4 (Monoamine Oxidase)
RN  - RML78EN3XE (Rimonabant)
RN  - TG537D343B (Desipramine)
SB  - IM
MH  - *Adaptation, Psychological
MH  - Animals
MH  - Biogenic Monoamines/analysis
MH  - Brain-Derived Neurotrophic Factor/genetics
MH  - Desipramine/pharmacology
MH  - Female
MH  - Hippocampus/chemistry
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Monoamine Oxidase/metabolism
MH  - Piperidines/pharmacology
MH  - Pyrazoles/pharmacology
MH  - RNA, Messenger/analysis
MH  - Receptor, Cannabinoid, CB1/antagonists & inhibitors/genetics/*physiology
MH  - Rimonabant
MH  - Signal Transduction/*physiology
MH  - Stress, Psychological/*psychology
MH  - Swimming
MH  - Vesicular Glutamate Transport Protein 1/genetics
EDAT- 2007/08/09 09:00
MHDA- 2008/07/02 09:00
CRDT- 2007/08/09 09:00
PHST- 2007/08/09 09:00 [pubmed]
PHST- 2008/07/02 09:00 [medline]
PHST- 2007/08/09 09:00 [entrez]
AID - 6500466 [pii]
AID - 10.1038/sj.tpj.6500466 [doi]
PST - ppublish
SO  - Pharmacogenomics J. 2008 Jun;8(3):196-208. doi: 10.1038/sj.tpj.6500466. Epub 2007 
      Aug 7.