Prenatal MAM treatment altered fear conditioning following social isolation: Relevance to schizophrenia.

Adolescent social isolation (SI) might change the trajectory of brain development. In the present study, we investigated the effect of short-term adolescent SI on fear memory, anxiety and protein levels in the adult medial prefrontal cortex of rats prenatally treated with methylazoxymethanol, MAM-E17 model of schizophrenia. The animals were maintained in standard housing (SH) or social isolation (P30-P40, SI) conditions. Behavioural tests (trace or delay fear conditioning, light/dark box) were performed in late adolescence and early adulthood. The results showed that MAM treatment did not alter fear memory, which was investigated with the use of either trace or delay fear conditioning, at any age, and SI decreased the fear response in adult control animals only under trace conditioning. Neither MAM nor SI influenced anxiety-related behaviour measured in the light/dark box. A proteomics study showed that both MAM and SI changed the protein levels related to synapse maturation and cytoskeletal organization, energy transfer and metabolic processes. Prenatal or adolescent environmental factors are able to change the expression of proteins that are correlated with behavioural impairments. Moreover, SI reversed some alterations in proteins induced by MAM. Thus, normally developing brains showed different responses to adolescent SI than those with altering courses of MAM administration.