Reduction of dopmamine D2 receptor binding in medial prefrontal cortex in schizophrenia animal model with maternal immune activation

Major Mental disorder such as schizophrenia is characterized by disturbances of thoughts, perception, cognition and volition. It is reported that about 1% of the world population becomes morbid with schizophrenia. However, the schizophrenia pathology and onset mechanism is not well known. Recently, it was reported that dopamine D2 receptor (D2R) binding decreases in medial prefrontal cortex (mPFC) in schizophrenia patient (Suhara T 2002). On the other hands, it has been indicated that maternal immune activation increases the risk of psychiatric disorder such as schizophrenia in offspring. These suggest possibility that maternal immune activation induces to disrupt dopaminergic system, which is then in schizophrenia pathology, in offspring. To test this hypothesis, we gave Toll-like receptor3 ligand synthetic double-stranded RNA polyriboinosinic-polyribocytidilic acid (Poly I:C) (0.4mg/kg/day), which mimic viral infection to cause immune activation, to pregnant rats on gestation days 15-18. And we investigated that D2R ligand (Carbon 11-labeled FLB457) binding potential in whole brain in mature offspring with Poly I:C treated dams, using positron emission tomography. As a result, the Carbon 11-labeled FLB457 binding potential significantly decreased in mPFC in mature offspring with Poly IC treated dams (P< 0.05). This result indicates a high degree of homology between animal model of schizophrenia with maternal immune activation and schizophrenia patient, in disruption of dopaminergic system. We suggest that maternal immune activation might evoke schizophrenia like pathology in adulthoods.第33回日本神経科学大会（Neuro2010