Adolescent Raloxifene Treatment in Females Prevents Cognitive Deficits in a Neurodevelopmental Rodent Model of Schizophrenia

The existence of sex differences in schizophrenia is a well documented phenomenon which led to the hypothesis that female sex hormones are neuroprotective and hence responsible for the more favorable disease characteristics seen in women. The current study sought to investigate the effects of estrogen-like agents administered during early adolescence on behavioral outcomes in adulthood using the neurodevelopmental maternal immune activation (MIA) rodent model of schizophrenia. Female MIA offspring were administered during the asymptomatic period of adolescence with either 17β-estradiol, raloxifene or saline and were tested in late adolescence and adulthood for schizophrenia-related behavioral performance. We report here that whereas adult female MIA offspring exhibited cognitive deficits in the form of retarded spatial learning, the administration of raloxifene during adolescence was sufficient in preventing these deficits and resulted in intact performance in the MIA group.