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Genetic inactivation of the CRF2 receptor eliminates morphine-induced sociability deficits in female mice

Year: 2025
Type: article
Abstract: Social behavior deficits, such as poor sociability and social isolation, are key clinical features of substance use disorders. The corticotropin-releasing factor (CRF) system may underlie the effects of substances of abuse but its implication in substance-induced social behavior deficits remains largely unknown. CRF signaling is mediated by two receptor types, termed CRF 1 and CRF 2 . Using the genetic mouse model of CRF 2 receptor-deficiency and the three-chamber task for sociability, the present studies examined the specific role for the CRF 2 receptor in sociability deficits induced by morphine. Notably, to assess possible sex-linked differences, female and male CRF 2 receptor wild-type (CRF 2 WT) or knockout (CRF 2 KO) mice were used. Intraperitoneal administration of morphine (1 mg/kg) reliably eliminated the preference for an unfamiliar same-sex conspecific over an object in female CRF 2 WT, but not in CRF 2 KO, mice, revealing a key role for the CRF 2 receptor in opiate-induced sociability deficits. In contrast, morphine almost significantly and similarly reduced the preference for an unfamiliar same-sex conspecific over an object in male CRF 2 WT and CRF 2 KO mice , indicating no role for the CRF 2 receptor. Notably, treatment with morphine never affected distance travelled during the three-chamber test, indicating that CRF 2 receptor-dependent or -independent opiate effects were specific to social behavior. The present findings provide initial evidence of a critical sex-linked role for the CRF 2 receptor in social behavior deficits induced by opiate substances, suggesting new, sex-customized, therapeutic strategy for opioid use disorders.
DOI: 10.1016/j.neuropharm.2025.110480
Language: English
Open Access status: hybrid
Estimated APC paid: $4,300
OpenAlex ID: W4409671584
FWCI: 0.343
Cites: 51
Cited by: 1
Related to: 10