Abstract
IntroductionPatients with schizophrenia have cognitive dysfunctions; positive psychotic symptoms are the primary purposes for schizophrenia treatment. Improvements in cognitive function should be a characteristic of all newly developed drugs for the treatment of schizophrenia with dementia. Thus, we investigated the effects of the second-generation antipsychotic ziprasidone, dopamine D1 antagonist SCH-23390 and dopamine D3 antagonist SB-277011 on spatial learning and memory. Materials and methodsMale inbred mice were used. The effects of ziprasidone, SCH-23390 and SB-277011 were investigated using the Morris water maze test. ResultsZiprasidone (0.5 and 1mg/kg), SCH-23390 (0.05 and 0.1mg/kg) and SB-277011 (10 and 20mg/kg) had no effect on the time spent in the target quadrant in naive mice. MK-801 (0.1mg/kg) significantly decreased the time spent in the target quadrant. The time spent in the target quadrant was significantly prolonged by Ziprasidone (0.5 and 1mg/kg) and SCH-23390 (0.1mg/kg), but not with SB-277011 (20mg/kg) in MK-801-treated mice.Ziprasidone (0.5 and 1mg/kg), SCH-23390 (0.05 and 0.1mg/kg) and SB-277011 (10 and 20mg/kg) had no effect on the mean distance to the platform in naive mice. MK-801 significantly increased the mean distance to the platform. Ziprasidone (1mg/kg) and SCH-23390 (0.1mg/kg) significantly decreased the mean distance to the platform in MK-801-treated mice, but SB-277011 (20mg/kg) didn't.MK-801 significantly increased the total distance moved. Ziprasidone (0.5 and 1mg/kg), SCH-23390 (0.05 and 0.1mg/kg) and SB-277011 (10 and 20mg/kg) had no effect on the total distance moved in naive mice. Ziprasidone (1mg/kg) and SCH-23390 (0.1mg/kg) significantly decreased the total distance moved in MK-801-treated mice, but SB-277011 (20mg/kg) didn't. ConclusionsThe second-generation antipsychotic drug ziprasidone and D1 antagonist SCH23390, but not the D3 antagonist SB277011, might be clinically useful for the treatment of cognitive impairments in patients with schizophrenia.
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