Objective: One of the most important problems of schizophrenic patients is the impairment of cognitive functions. Methods: The aim of this study was to investigate the effects of haloperidol, asenapine and paliperidone on spatial learning and memory using the Morris water maze (MWM) and radial arm maze (RAM) tests; moreover the effects of haloperidol, asenapine, and paliperidone on MK-801 induced cognitive dysfunction were also evaluated in mice. Results: Both asenapine (0.05 mg/kg) and paliperidone reversed MK-801 induced increment in escape latency in 2nd, 3rd, and 4th acquisition sessions while haloperidol failed to reverse MK-801 induced this effect. Time spent in escape platform’s quadrant significantly decreased while the mean distance to platform significantly increased in MK-801 group in the probe trial of MWM test and administration of asenapine and paliperidone significantly reversed MK- 801 induced these effects while haloperidol had no effect. MK-801 significantly increased the speed of the animals in probe trial of the MWM test while both asenapine and paliperidone reversed this effect. In the RAM test, MK- 801 significantly increased the number of errors in the retention trial and haloperidol failed to reverse this effect. Both asenapine (0.075 mg/kg) and paliperidone reversed MK-801-induced increment in a number of errors and improved MK-801 induced prolongation in latency. Conclusions: The results of this study revealed that MK-801 exerted spatial memory impairment in MWM and RAM tests; haloperidol failed to improve MK-801 induced memory deterioration in mice. Moreover both asenapine and paliperidone improved MK-801 induced spatial learning and memory impairment in the MWM and RAM tests.
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