CRF2 null mutation increases sensitivity to isolation rearing effects on locomotor activity in mice

Jodi Gresack, Susan Powell, Mark Geyer, Mary Stenzel Poore, Sarah Coste, Victoria Risbrough

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Background: Developmental stressors are consistently reported to increase risk for certain neuropsychiatric disorders including schizophrenia, depression, and post-traumatic stress disorder. Recent clinical evidence supports a " double-hit" hypothesis of genetic vulnerability interacting with developmental challenges to modulate this risk. Early life stressor effects on behavior may be modulated in part by alterations in corticotropin releasing factor (CRF) signaling via two known receptors, CRF1 and CRF2. One extant hypothesis is that CRF2 activation may modulate long-term adaptive responses after homeostatic challenge. As such, loss of CRF2 activity via genetic variance may increase sensitivity to the long-term effects of developmental stress. Methods: We tested the hypothesis that CRF2 function may mitigate the behavioral effects of isolation rearing, predicting that loss of CRF2 function increases sensitivity to this developmental challenge. Using the behavioral pattern monitor (BPM), we examined exploratory behavior and locomotor patterns in adult CRF2 wild-type (WT) and gene knockout (KO) mice reared socially or in isolation. Results: Isolation housing produced robust increases in the amount of locomotor activity and investigatory holepoking, and altered the temporal distribution of activity in CRF2 KO but not CRF2 WT mice. Isolation housing significantly increased rearing behavior and altered spatial patterns of locomotor activity regardless of genotype. Conclusions: Loss of CRF2 function increased sensitivity to the effects of chronic social isolation on exploratory locomotor behavior. Thus, CRF2 activation appears to mitigate isolation rearing effects on exploratory behavior. Further research assessing the interaction between CRF2 function and developmental challenges is warranted.

Original languageEnglish (US)
Pages (from-to)349-353
Number of pages5
JournalNeuropeptides
Volume44
Issue number4
DOIs
StatePublished - Aug 1 2010

Keywords

  • CRF
  • CRH
  • Developmental stress
  • Isolation rearing
  • Locomotor activity
  • Schizophrenia
  • Social isolation

ASJC Scopus subject areas

  • Endocrinology
  • Neurology
  • Endocrine and Autonomic Systems
  • Cellular and Molecular Neuroscience

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