Innovation of an animal model for the pathophysiology of schizophrenia

: The pharmacological treatment of schizophrenia now faces a turning point where we are preparing for the introduction of medications which have the mechanism of modulating glutamatergic neurotransmission, in contrast to antipsychotics which have the main mechanism of blocking and modulating D2-type dopamine receptor-mediated dopaminergic neurotransmission. In order to predict the effects of new medications modulating glutamatergic neurotransmission, we have to understand the pathophysiology of schizophrenia in the light of the dynamic time-axis. In the present review article, we have proposed a new "comprehensive progressive pathophysiology model" based on the "dopamine to glutamate hypothesis". Using this model, we distinguish the progressive pathophysiology-stage and subsequent residual-stage, to predict the effects of antipsychotics, mood stabilizers, and new glutamatergic modulators.