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

Affiliations
  • 1Paik Institute for Clinical Research, Graduate School, Inje University, Busan, Korea. iybihwc@naver.com
  • 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.

Abstract


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.

Keyword

Olanzapine; Haloperidol; Memory; NMDA antagonist; Neurogenesis

MeSH Terms

Animals
Antipsychotic Agents
Behavior Rating Scale
Bromodeoxyuridine
Cognition Disorders
Dentate Gyrus
Dizocilpine Maleate
Haloperidol*
Hippocampus
Humans
Immunohistochemistry
Infant, Newborn
Memory*
Mice*
Neurogenesis
Spatial Memory
Water
Antipsychotic Agents
Bromodeoxyuridine
Dizocilpine Maleate
Haloperidol
Water
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