Adolescent Social Isolation Affects Schizophrenia-Like Behavior in the MAM-E17 Model of Schizophrenia

Abstract

Social isolation (SI) during adolescence may induce schizophrenia-like behavior. In the present study, we investigated whether adolescent SI might affect the development of schizophrenia-like behavior in the MAM-E17 neurodevelopmental model of schizophrenia. Rats were socially isolated for 10 days during adolescence (postnatal days (P) 30-40), followed by resocialization until late adolescence (P45-P48) or early adulthood (P70-P75); behavioral and neurochemical studies were performed at these ages. The behavioral studies analyzed locomotor activity, social interaction, recognition memory, and sensorimotor gating; GAD65 and GAD67 protein levels were measured in the prefrontal cortex. The results showed that SI did not affect locomotor activity, but it prevented the social interaction deficits induced by MAM administration at both of the analyzed age points. However, SI induced a deficit in recognition memory in the MAM group during adolescence, which was not observed in the MAM-treated, socially housed rats at this age. In adulthood, impairments in recognition memory were detected in both MAM groups. In contrast, SI did not accelerate the appearance of sensorimotor gating deficits in MAM animals during adolescence, and sensorimotor gating impairments were observed in both MAM groups during adulthood. Adolescent SI rearing did not affect any examined behavioral responses in the VEH-treated groups. SI altered the levels of GAD65 and GAD67 proteins during adolescence in both groups; however, the decrease in the level of GAD65 protein was observed only in the adult MAM-SI group. Thus, SI rearing during a defined period of adolescence might have specific effects on the emergence of schizophrenia-like abnormalities in MAM-treated animals.

Keywords: Adolescence; Cognition; Development; Schizophrenia; Social behavior.