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Differential Effects of Olanzapine and Haloperidol on MK-801-induced Memory Impairment in Mice
Jae Chun Song1, Mi Kyoung Seo1, Sung Woo Park1,2
1Paik Institute for Clinical Research, Inje University, Busan, Korea.
Objective:
We investigated the differential effects of the antipsychotic drugs olanzapine and haloperidol on MK-801-induced memory impairment and neurogenesis in mice.
Methods:
MK-801 (0.1 mg/kg) was administered 20 minutes prior to behavioral testing over 9 days. Beginning on the sixth day of MK-801 treatment, either olanzapine (0.05 mg/kg) or haloperidol (0.05 mg/kg) was administered 40 minutes prior to MK-801 for the final 4 days. Spatial memory performance was measured using a Morris water maze (MWM) test for 9 days (four trials/day). Immunohistochemistry with bromodeoxyuridine (BrdU) was used to identify newborn cells labeled in tissue sections from the dentate gyrus of the hippocampus.
Results:
MK-801 administration over 9 days significantly impaired memory performance in the MWM test compared to untreated controls (p＜0.05) and these deficits were blocked by treatment with olanzapine (p＜0.05) but not haloperidol. The administration of MK-801 also resulted in a decrease in the number of BrdU-labeled cells in the dentate gyrus (28.6%; p＜0.01), which was prevented by treatment with olanzapine (p＜0.05) but not haloperidol.
Conclusion:
These results suggest that olanzapine has a protective effect against cognitive impairments induced by MK-801 in mice via the stimulating effects of neurogenesis.
