The postweaning social isolation in C57BL/6 mice: preferential vulnerability in the male sex.
BACKGROUND
Social deprivation during early life can severely affect mental health later in adulthood, leading to the development of behavioural traits associated with several major psychiatric disorders including schizophrenia. This has led to the application of social isolation in laboratory animals to model the impact of environmental factors on the aetiopathology of schizophrenia. However, controversy exists over the precise behavioural profile and the robustness of some of the reported effects of social isolation rearing.


METHODS
Here, we evaluated the efficacy of postweaning social isolation to induce schizophrenia-related behavioural deficits in C57BL/6 mice of both sexes.


RESULTS
The effects of social isolation clearly differed between sexes: isolated male but not female mice exhibited multiple habituation deficits and enhanced locomotor reaction to amphetamine.


CONCLUSIONS
The preferential vulnerability in the male sex corresponds well with the earlier disease onset and poorer prognosis in male relative to female schizophrenic patients. In contrast, we observed no evidence for a disruption of sensorimotor gating in the prepulse inhibition paradigm despite the efficacy of social isolation to alter startle reactivity. With both success and failure in the induction of schizophrenia-related endophenotypes, the present study thus provides important characterizations and qualifications to the application of the social isolation model in mice.


CONCLUSIONS
We conclude that social isolation in mice represents a valuable tool for the examination of candidate genes within the context of the "two-hit" hypothesis of the aetiological processes in schizophrenia.
Pietropaolo
Susanna
S
Laboratory of Behavioural Neurobiology, Swiss Federal Institute of Technology Zurich, Schorenstrasse 16, CH-8603 Schwerzenbach, Switzerland.
Singer
Philipp
P
Feldon
Joram
J
Yee
Benjamin K
BK
D000818:Animals; D003423:Critical Period, Psychological; D004195:Disease Models, Animal; D005239:Fear; D005260:Female; D006185:Habituation, Psychophysiologic; D006801:Humans; D008297:Male; D018782:Maze Learning; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity; D013216:Reflex, Startle; D012307:Risk Factors; D012565:Schizophrenic Psychology; D012737:Sex Factors; D012934:Social Isolation; D014886:Weaning