Sex‐linked roles of the CRF1 and the CRF2 receptor in social behavior. Issue 8 (29th May 2020)

• Record Type: Journal Article
• Authors: Piccin, Alessandro; Contarino, Angelo
• Is Part Of: Journal of neuroscience research. Volume 98:Issue 8(2020)
• Page Start: 1561
• Page End: 1574
• Publication Date: 2020-05-29
• Subjects: corticotropin‐releasing factor (CRF) -- CRF1 receptor -- CRF2 receptor -- mice -- sex -- sociability -- social odor preference; Neurobiology -- Periodicals; 612
• DOI: 10.1002/jnr.24629
• Languages: English
• ISSNs: 0360-4012

Abstract

Abstract: Dysfunctional social behavior is a major clinical feature of mood, anxiety, autism spectrum, and substance‐related disorders, and may dramatically contribute to the poor outcome of these diseases. Nevertheless, the mechanisms underlying social behavior deficits are still largely unknown. The corticotropin‐releasing factor (CRF) system, a major coordinator of the stress response, has been hypothesized to modulate social behavior. CRF signaling is mediated by two receptor types, termed CRF1 and CRF2 . Using the three‐chamber task for sociability (i.e., preference for an unfamiliar conspecific vs. an object), this study demonstrates that CRF2 receptor null mutation (CRF2 −/−) reduces sociability in female mice but increases it in male mice. Both female and male CRF2 −/− mice display a preference for social odor cues over neutral cues, indicating that sex‐ and CRF2 receptor‐dependent sociability is not due to altered olfaction or impaired social cues discrimination. Moreover, treatment with the CRF1 receptor‐preferring antagonist, antalarmin, consistently induces sociability in non‐social mice but disrupts it in social mice, independently of CRF2 receptor deficiency. Sex, CRF2 receptor deficiency, or antalarmin affect locomotor activity during the three‐chamber test. However, throughout the study CRF1 and CRF2 receptor‐linked sociability is independent of locomotor activity. The present findings highlight major functions for the CRF system in the regulation of social behavior. Moreover, they provide initial evidence of sex‐linked roles for the CRF1 and the CRF2 receptor, emphasizing the importance of sex as a major biological variable to be taken into consideration in preclinical and clinical studies. Abstract : Corticotropin‐releasing factor (CRF) signaling is mediated by two receptor types, CRF1 and CRF2 . Herein, we demonstrate that genetic CRF2 receptor deficiency (CRF2 −/−) reduces sociability in female mice but increases it in male mice. Moreover, the CRF1 receptor‐preferring antagonist antalarmin reverses sociability in both female and male wild‐type (CRF2 +/+) and CRF2 −/− mice.