Risperidone Administered During Asymptomatic Period of Adolescence Prevents the Emergence of Brain Structural Pathology and Behavioral Abnormalities in an Animal Model of Schizophrenia

摘要: Schizophrenia is a disorder of neurodevelopmental origin manifested symptomatically after puberty. Structural neuroimaging studies show that neuroanatomical aberrations precede onset symptoms, raising question whether schizophrenia can be prevented. Early treatment with atypical antipsychotics may reduce the risk transition to psychosis, but it remains unknown abnormalities We have recently shown, using in vivo structural magnetic resonance imaging, antipsychotic clozapine during an asymptomatic period adolescence prevents emergence schizophrenia-like brain adult rats exposed prenatal immune challenge, parallel preventing behavioral abnormalities. Here we assessed preventive efficacy risperidone (RIS). Pregnant were injected on gestational day 15 viral mimic polyriboinosinic-polyribocytidylic acid (poly I:C) or saline. Their male offspring received daily RIS (0.045 1.2 mg/kg) vehicle injection peri-adolescence (postnatal days [PND] 34–47). changes and behavior at adulthood (from PND 90). Adult poly I:C–treated dams exhibited hallmark associated schizophrenia, enlarged lateral ventricles smaller hippocampus. Both these absent I:C peri-adolescence. This was paralleled by prevention abnormalities, attentional deficit, hypersensitivity amphetamine offspring. conclude pharmacological intervention prevent pathology resulting from utero insult. Furthermore, highly selective 5HT2A receptor antagonists promising targets for psychosis prevention.