Study On Screening Of New Antischizophrenic Drugs Using Mouse Model

The schizophrenia-like mouse model has been established in our laboratory. In the model the major evaluation factors are hyperlocomotion and stereotypy behaviors, and the auxiliary indications are rearing and hole-exploring behaviors. The primary work involved in this dissertation is to screen the drugs that may have antischizophrenic activity in opioid antagonists and dopamine D3 antagonist using the schizophrenia mouse model. The results suggest that β-FNA, a μopioid receptor irreversible antagonist, can alleviate evidently the psychotomimetic symptoms of ICR schizophrenia-like mice, which could be stated in detail as follows: β-FNA markedly reduces the time length for doing stereotypy and ameliorate remarkably the mice's rearing behavior. The drug also resumes to some degree the schizophrenia-like mice's memory and recognition ability. Dopamine D3 antagonist PG 1037 can markedly antagonize the schizophrenia-like mice's stereotypy behavior of C57BL/6 and ICR strains and reduce the hyperlocomotion activity of the schizophrenia-like mice of ICR strain. The k receptor antagonist nor-BNI and highly selective δreceptor antagonist NTI have no observable effects on psychotomimetic symptoms of the schizophrenia-like mice. To sum up, the μreceptor antagonist β-FNA and D3 receptor antagonist PG 1037 have so markedly an antischizophrenic activity as to be further studied, and developed to be used clinically.