Effects of haloperidol, olanzapine, ziprasidone, and PHA-543613 on spatial learning and memory in the Morris water maze test in naïve and MK-801-treated mice.

INTRODUCTION

Cognitive impairment is the core symptom of schizophrenia, significantly impacting the functional outcome. Improvement of cognitive function has been an important aspect of the treatment of schizophrenia. Therefore, this study is to demonstrate the effects of first-generation antipsychotic haloperidol, second-generation antipsychotic olanzapine and ziprasidone, and alpha-7 nicotinic acetylcholine receptor agonist PHA-543613 on spatial learning and memory.

MATERIAL AND METHODS

C57BL/6 mice received intraperitoneal injections of haloperidol (2 mg/kg), olanzapine (2.5 mg/kg), ziprasidone (2 mg/kg), and PHA-543613 (1 mg/kg), and cognitive dysfunctions were induced by MK-801 (0.1 mg/kg). Morris water maze was used for investigating the effects of all agents.

RESULTS

Mk-801 significantly increased the mean escape latency to the platform and decreased the number of platform area crossings. Ziprasidone had no effect on the mean escape latency to platform and the number of platform area crossings in naïve mice, but haloperidol, olanzapine, and PHA-543613 did not. Haloperidol and olanzapine significantly increased the mean escape latency to platform and decreased the number of platform area crossings, while ziprasidone and PHA-543613 did not. All the agents had no effect on swimming speed.

CONCLUSIONS

Ziprasidone and alpha-7 nicotinic acetylcholine receptor agonist PHA-543613 might be helpful in the treatment of CIAS.