Effects of social isolation rearing on the limbic brain: a combined behavioral and magnetic resonance imaging volumetry study in rats.

Rearing rats in social isolation from weaning induces robust behavioral and neurobiological alterations resembling some of the core symptoms of schizophrenia, such as reduction in prepulse inhibition of acoustic startle (PPI) and locomotor hyperactivity in a novel arena. The aim of this study was to investigate whether social isolation rearing induces volumetric remodeling of the limbic system, and to probe for anatomical structure-behavioral interrelations. Isolation- (n=8) and group-reared (n=8) rats were examined by magnetic resonance (MR) volumetry using high-resolution T2-weighted imaging at 7 T. Volumes of medial prefrontal cortex (mPFC), anterior cingulate cortex (ACC), retrosplenial cortex (RSC) and hippocampal formation were compared between groups and with behavioral measures, i.e. PPI and locomotor activity in a novel arena. Isolation rearing induced locomotor hyperactivity and impaired PPI compared with group-housed rats. The right mPFC was significantly reduced (5.4%) in isolation-reared compared with group-reared rats, with a similar trend on the left side (5.2%). mPFC volumes changes were unrelated to behavioral abnormalities. No significant volume changes were observed in ACC, RSC or hippocampal formation. Hippocampal volumes were associated with the magnitude of PPI response in control but not in isolation-reared rats. Rearing rats in social isolation induced remodeling of the limbic brain with selective prefrontal cortex volume loss. In addition, a dissociation of the interrelation between hippocampal volume and PPI was noted in the isolation-reared rats. Taken together, limbic morphometry is sensitive to the effects of social isolation rearing but did not reveal direct brain-behavior interrelations, calling for more detailed circuitry analysis.