CRF2 null mutation increases sensitivity to isolation rearing effects on locomotor activity in mice.
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, CRF(1) and CRF(2). One extant hypothesis is that CRF(2) activation may modulate long-term adaptive responses after homeostatic challenge. As such, loss of CRF(2) activity via genetic variance may increase sensitivity to the long-term effects of developmental stress.


METHODS
We tested the hypothesis that CRF(2) function may mitigate the behavioral effects of isolation rearing, predicting that loss of CRF(2) function increases sensitivity to this developmental challenge. Using the behavioral pattern monitor (BPM), we examined exploratory behavior and locomotor patterns in adult CRF(2) 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 CRF(2) KO but not CRF(2) WT mice. Isolation housing significantly increased rearing behavior and altered spatial patterns of locomotor activity regardless of genotype.


CONCLUSIONS
Loss of CRF(2) function increased sensitivity to the effects of chronic social isolation on exploratory locomotor behavior. Thus, CRF(2) activation appears to mitigate isolation rearing effects on exploratory behavior. Further research assessing the interaction between CRF(2) function and developmental challenges is warranted.
Gresack
Jodi
J
Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093-0804, USA.
Powell
Susan
S
Geyer
Mark
M
Poore
Mary-Stenzel
MS
Coste
Sarah
S
Risbrough
Victoria
V
D000818:Animals; D005106:Exploratory Behavior / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology*; D009154:Mutation / Q000502:physiology; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics*; D012931:Social Environment; D012934:Social Isolation; D013315:Stress, Psychological / Q000235:genetics / Q000523:psychology
C101531:CRF receptor type 2; D018019:Receptors, Corticotropin-Releasing Hormone
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