title: Corticotropin-releasing factor receptor antagonism within the dorsal raphe nucleus reduces social anxiety-like behavior after early-life social isolation.
abstract: 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.
authors.affiliation: University of South Dakota, Vermillion, 57069, USA.
authors.forename: Jodi
authors.initials: J
authors.lastname: Lukkes
authors.forename: Shawn
authors.initials: S
authors.lastname: Vuong
authors.forename: Jamie
authors.initials: J
authors.lastname: Scholl
authors.forename: Harvey
authors.initials: H
authors.lastname: Oliver
authors.forename: Gina
authors.initials: G
authors.lastname: Forster
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001007:Anxiety / Q000188:drug therapy*; D002404:Catheterization; D003346:Corticotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000494:pharmacology; D008124:Locomotion / Q000187:drug effects; D008297:Male; D011903:Raphe Nuclei / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D012919:Social Behavior; D012934:Social Isolation; D013997:Time Factors
chemical_list: D018019:Receptors, Corticotropin-Releasing Hormone; C113202:phenylalanyl corticotropin-releasing factor (12-41); D003346:Corticotropin-Releasing Hormone
references.citation: Eur J Pharmacol. 2008 Jan 14;578(2-3):185-93
references.pmid: 17945210
references.citation: Neuropsychopharmacology. 2000 Mar;22(3):230-9
references.pmid: 10693150
references.citation: Brain Res. 1996 Sep 2;732(1-2):145-53
references.pmid: 8891278
references.citation: Behav Neurosci. 1989 Jun;103(3):648-54
references.pmid: 2786722
references.citation: Horm Behav. 1987 Jun;21(2):193-202
references.pmid: 2886414
references.citation: Psychopharmacology (Berl). 2007 Oct;194(3):297-307
references.pmid: 17581742
references.citation: Horm Behav. 2005 Jun;48(1):1-10
references.pmid: 15919381
references.citation: J Neurosci Methods. 1980 Dec;3(2):129-49
references.pmid: 6110810
references.citation: Neuroscience. 2007 Jun 8;146(4):1888-905
references.pmid: 17467184
references.citation: J Neurosci. 1995 Oct;15(10):6340-50
references.pmid: 7472399
references.citation: J Neurosci. 2006 Sep 6;26(36):9142-52
references.pmid: 16957071
references.citation: J Neurosci. 2004 Feb 11;24(6):1305-11
references.pmid: 14960601
references.citation: Neuroscience. 2009 Jan 23;158(2):845-55
references.pmid: 19010398
references.citation: Crit Rev Neurobiol. 1998;12(1-2):129-62
references.pmid: 9444483
references.citation: Psychopharmacol Bull. 2004 Winter;38(1):14-20
references.pmid: 15278013
references.citation: Neuroscience. 2006 Aug 25;141(2):1047-1055
references.pmid: 16713119
references.citation: J Pharmacol Exp Ther. 1999 Feb;288(2):729-34
references.pmid: 9918582
references.citation: J Neurosci. 1999 Oct 15;19(20):RC35
references.pmid: 10516337
references.citation: Horm Behav. 2009 Jan;55(1):248-56
references.pmid: 19027017
references.citation: Neurosci Biobehav Rev. 2003 Jan-Mar;27(1-2):3-18
references.pmid: 12732219
references.citation: Eur J Pharmacol. 2005 Feb 21;509(2-3):145-53
references.pmid: 15733549
references.citation: Brain Res. 1992 May 29;581(2):190-7
references.pmid: 1327398
references.citation: Brain Res. 2001 Jun 1;902(2):135-42
references.pmid: 11384606
references.citation: J Pharmacol Exp Ther. 2002 Jul;302(1):145-52
references.pmid: 12065711
references.citation: Stress. 2005 Dec;8(4):233-46
references.pmid: 16423712
references.citation: J Neurosci. 2001 Apr 15;21(8):2833-41
references.pmid: 11306635
references.citation: J Pharmacol Exp Ther. 1999 May;289(2):926-35
references.pmid: 10215672
references.citation: Neuroscience. 2006;138(4):1265-76
references.pmid: 16488545
references.citation: Neuroscience. 2004;129(3):509-19
references.pmid: 15541873
references.citation: Horm Behav. 2001 May;39(3):195-205
references.pmid: 11300710
references.citation: Dev Psychobiol. 1999 Mar;34(2):129-38
references.pmid: 10086231