Impaired cannabinoid receptor type 1 signaling interferes with stress-coping behavior in mice.
Pharmacogenomics J. 2007-08-07; 8(3): 196-208
DOI: 10.1038/sj.tpj.6500466
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1. Pharmacogenomics J. 2008 Jun;8(3):196-208. Epub 2007 Aug 7.
Impaired cannabinoid receptor type 1 signaling interferes with stress-coping
behavior in mice.
Steiner MA(1), Wanisch K, Monory K, Marsicano G, Borroni E, Bächli H, Holsboer F,
Lutz B, Wotjak CT.
Author information:
(1)Max Planck Institute of Psychiatry, Munich, Germany.
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.
DOI: 10.1038/sj.tpj.6500466
PMID: 17684478 [Indexed for MEDLINE]