Corticotropin-releasing factor receptor 2-deficiency eliminates social behaviour deficits and vulnerability induced by cocaine.
Br J Pharmacol
; 175(9): 1504-1518, 2018 05.
Article
in En
| MEDLINE
| ID: mdl-29406581
ABSTRACT
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. EXPERIMENTALAPPROACH:
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. KEYRESULTS:
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Social Behavior
/
Stress, Psychological
/
Substance Withdrawal Syndrome
/
Cocaine
/
Receptors, Corticotropin-Releasing Hormone
Aspects:
Determinantes_sociais_saude
Limits:
Animals
Language:
En
Journal:
Br J Pharmacol
Year:
2018
Document type:
Article
Affiliation country:
France