Pharmacological studies on animal models of Alzheimer disease and Senile dementia, and development of therapeutic drugs

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1. Animal models of alzheimer disease and senile dementia, and behavioral changes(1) In rats treated with vincristine into the nuilateral striatum, apomorphine produced transient rotational behavior 2 to 3 days agter the treatment.(2) Microinjection of vincristine into the bilateral striata prevented the acquisition and retention of spatial memory of rats 3 to 5 days after the injection. Since these rats died due to the paralysis of four legs by two to four weeks after the injection, vincristine-induced lesion was considered to be progressive.2. Changes of neurotransmitters in the striatum of the model animals(1) Measurement of catecholamines: Striatal dopamine and its metabolites slightly decreased 7 to 8 days after the intrastriatal microinjection of vincristine.(2) receptor binding assay: [^3H]-spiperone binding to striatal membranes decreased after vincristine treatment. Further investigation is required to clarify if an animal model of alzheimer disease is sensitive to drugs.