Genetic dissection of the role of cannabinoid type-1 receptors in the emotional consequences of repeated social stress in mice.
Neuropsychopharmacol. 2012-03-21; 37(8): 1885-1900
DOI: 10.1038/npp.2012.36
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1. Neuropsychopharmacology. 2012 Jul;37(8):1885-900. doi: 10.1038/npp.2012.36. Epub
2012 Mar 21.
Genetic dissection of the role of cannabinoid type-1 receptors in the emotional
consequences of repeated social stress in mice.
Dubreucq S(1), Matias I, Cardinal P, Häring M, Lutz B, Marsicano G, Chaouloff F.
Author information:
(1)Team ‘Endocannabinoids and NeuroAdaptation’, INSERM U862, NeuroCentre
Magendie, Bordeaux, France.
The endocannabinoid system (ECS) tightly controls emotional responses to acute
aversive stimuli. Repeated stress alters ECS activity but the role played by the
ECS in the emotional consequences of repeated stress has not been investigated in
detail. This study used social defeat stress, together with pharmacology and
genetics to examine the role of cannabinoid type-1 (CB(1)) receptors on repeated
stress-induced emotional alterations. Seven daily social defeat sessions
increased water (but not food) intake, sucrose preference, anxiety, cued fear
expression, and adrenal weight in C57BL/6N mice. The first and the last social
stress sessions triggered immediate brain region-dependent changes in the
concentrations of the principal endocannabinoids anandamide and
2-arachidonoylglycerol. Pretreatment before each of the seven stress sessions
with the CB(1) receptor antagonist rimonabant prolonged freezing responses of
stressed mice during cued fear recall tests. Repeated social stress abolished the
increased fear expression displayed by constitutive CB(1) receptor-deficient
mice. The use of mutant mice lacking CB(1) receptors from cortical glutamatergic
neurons or from GABAergic neurons indicated that it is the absence of the former
CB(1) receptor population that is responsible for the fear responses in socially
stressed CB(1) mutant mice. In addition, stress-induced hypolocomotor reactivity
was amplified by the absence of CB(1) receptors from GABAergic neurons. Mutant
mice lacking CB(1) receptors from serotonergic neurons displayed a higher anxiety
but decreased cued fear expression than their wild-type controls. These mutant
mice failed to show social stress-elicited increased sucrose preference. This
study shows that (i) release of endocannabinoids during stress exposure impedes
stress-elicited amplification of cued fear behavior, (ii) social stress opposes
the increased fear expression and delayed between-session extinction because of
the absence of CB(1) receptors from cortical glutamatergic neurons, and (iii)
CB(1) receptors on central serotonergic neurons are involved in the sweet
consumption response to repeated stress.
DOI: 10.1038/npp.2012.36
PMCID: PMC3376321
PMID: 22434220 [Indexed for MEDLINE]