Article date: May 2018
By: Nadège Morisot, Romain Monier, Catherine Le Moine, Mark J Millan, Angelo Contarino in Volume 175, Issue 9, pages 1504-1518
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.
DOI: 10.1111/bph.14159
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