Corticotropin-releasing factor receptor 2-deficiency eliminates social behaviour deficits and vulnerability induced by cocaine.
British Journal of Pharmacology. 2018-03-13; 175(9): 1504-1518
DOI: 10.1111/bph.14159
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1. Br J Pharmacol. 2018 May;175(9):1504-1518. doi: 10.1111/bph.14159. Epub 2018 Mar
13.
Corticotropin-releasing factor receptor 2-deficiency eliminates social behaviour
deficits and vulnerability induced by cocaine.
Morisot N(1)(2), Monier R(1)(2), Le Moine C(1)(2), Millan MJ(3), Contarino
A(1)(2).
Author information:
(1)INCIA, UMR 5287, Univ. Bordeaux, Bordeaux, France.
(2)INCIA, UMR 5287, CNRS, Bordeaux, France.
(3)Centre for Therapeutic Innovation in Neuropsychiatry, Institut de Recherches
Servier, Croissy-sur-Seine, France.
BACKGROUND AND PURPOSE: Poor social behaviour and vulnerability to stress are
major clinical features of stimulant use disorders. The corticotropin-releasing
factor (CRF) system mediates stress responses and might underlie substance use
disorders; however, its involvement in social impairment induced by stimulant
substances remains unknown. CRF signalling is mediated by two receptor types,
CRF1 and CRF2 . In the present study we investigated the role of the CRF2
receptor in social behaviour deficits, vulnerability to stress and related brain
alterations induced by cocaine administration and withdrawal.
EXPERIMENTAL APPROACH: CRF2 receptor-deficient (CRF2 -/-) and littermate
wild-type mice were repeatedly tested in the three-chamber task for sociability
(i.e. preference for an unfamiliar conspecific vs. an object) and social novelty
preference (SNP; i.e. preference for a novel vs. a familiar conspecific) before
and after chronic cocaine administration. An in situ hybridization assay was used
to assess gene expression of the stress-responsive arginine vasopressin (AVP) and
oxytocin (OT) neuropeptides in the hypothalamus.
KEY RESULTS: CRF2 receptor deficiency eliminated the sociability deficit induced
by cocaine withdrawal. Moreover, CRF2 -/- mice did not show either the
stress-induced sociability deficit or the increased AVP and OT expression
associated with long-term cocaine withdrawal, indicating resilience to stress.
Throughout, wild-type and CRF2 -/- mice displayed SNP, suggesting that cocaine
withdrawal-induced sociability deficits were not due to impaired detection of
social stimuli.
CONCLUSIONS AND IMPLICATIONS: These findings demonstrate a central role for the
CRF2 receptor in social behaviour deficits and biomarkers of vulnerability
induced by cocaine withdrawal, suggesting new therapeutic strategies for
stimulant use disorders.
© 2018 The British Pharmacological Society.
DOI: 10.1111/bph.14159
PMCID: PMC5900993 [Available on 2019-05-01]
PMID: 29406581