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

• Song JC
• Seo MK
• Park SW
• Lee JG
• Kim YH

• KMID: 2348476
• DOI: http://doi.org/10.9758/cpn.2016.14.3.279

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