Clin Psychopharmacol Neurosci.  2016 Aug;14(3):279-285. 10.9758/cpn.2016.14.3.279.

Differential Effects of Olanzapine and Haloperidol on MK-801-induced Memory Impairment in Mice

  • 1Paik Institute for Clinical Research, Graduate School, Inje University, Busan, Korea.
  • 2Department of Health Science and Technology, Graduate School, Inje University, Busan, Korea.
  • 3Department of Psychiatry, Inje University Haeundae Paik Hospital, Inje University School of Medicine, 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.
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.
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.
These results suggest that olanzapine has a protective effect against cognitive impairments induced by MK-801 in mice via the stimulating effects of neurogenesis.


Olanzapine; Haloperidol; Memory; NMDA antagonist; Neurogenesis
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