Corticotropin-releasing factor receptor antagonism within the dorsal raphe nucleus reduces social anxiety-like behavior after early-life social isolation

Jodi Lukkes, Shawn Vuong, Jamie Scholl, Harvey Oliver, Gina Forster

Research output: Contribution to journalArticle

59 Scopus citations


Social isolation of rats during the early part of development increases social anxiety-like behavior in adulthood. Furthermore, early-life social isolation increases the levels of corticotropin-releasing factor (CRF) receptors in the serotonergic dorsal raphe nucleus (dRN) of adult rats. Interactions between serotonin and CRF systems are thought to mediate anxiety behavior. Therefore, we investigated the effects of CRF receptor antagonism within the dRN on social anxiety-like behavior after early-life social isolation. Male rats were reared in isolation or in groups from weaning until midadolescence, and rehoused in groups and allowed to develop into adulthood. Adult rats underwent surgery to implant a drug cannula into the dRN. After recovery from surgery and acclimation to the testing arena, rats were infused with vehicle or the CRF receptor antagonist D-Phe-CRF(12-41) (50 or 500 ng) into the dRN before a social interaction test. Isolation-reared rats pretreated with vehicle exhibited increased social anxiety-like behavior compared with rats reared in groups. Pretreatment of the dRN with D-Phe-CRF(12-41) significantly reduced social anxiety-like behaviors exhibited by isolation-reared rats. Overall, this study shows that early-life social stress results in heightened social anxiety-like behavior, which is reversed by CRF antagonism within the dRN. These data suggest that CRF receptor antagonists could provide a potential treatment of stress-related social anxiety.

Original languageEnglish (US)
Pages (from-to)9955-9960
Number of pages6
JournalJournal of Neuroscience
Issue number32
StatePublished - Aug 12 2009


ASJC Scopus subject areas

  • Neuroscience(all)

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