Schizophrenia is a severe and common psychiatric disease with a lifetime prevalence of 0.5% to 1% globally. Because of limitations of the experimental approach in humans, valid animal models are essential in the effort to identify novel therapeutics for schizophrenia. In most animal models of schizophrenia, second generation antipsychotic drugs are reported to be effective in ameliorating behavioral abnormalities, while clinical evidence indicates that some of the patients are resistant to the antipsychotic drug therapy. Accordingly, animal models of antipsychotic drug-resistant schizophrenia are needed for screening of novel agents that may be more effective than the existing antipsychotic drugs. Furthermore, utilization of appropriate behavioral tasks with reference to human testing is essential to facilitate the development of novel pharmacotherapeutic approaches for the treatment in schizophrenia. Experimental data suggest that there are different types of potential candidate molecules as novel antipsychotic drugs with some therapeutic effects on negative symptoms and cognitive deficits in schizophrenia. It is proposed that to develop novel antipsychotic drugs the efficacy of potential candidate molecules should be evaluated using animal models for treatment-resistant schizophrenia with appropriate behavioral tasks in reference to human testing.
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