Effects of acute treatment of dizocilpine maleate on locomotor activity, prepulse inhibition and object recognition memory in rats

Abstract

Objective To investigate the effects of acute administration of dizocipline maleate (MK-801), the N-methyl-D-aspartate (NMDA) receptor antagonist, on locomotor activity, sensorimotor gating and object recognition memory in rats and to determine the appropriate doses for modelling each above-mentioned endophenotypes of schizophrenia. Methods Adult male Sprague-Dawley (SD) rats (n=104) received an intraperitoneal injection of either different dosage of MK-801 or saline 20 min prior to daily behavioral testing. (1) To investigate the effects of acute treatment of MK-801 (0.1, 0.2, 0.4 mg/kg) on locomotor activity. (2) To investigate the effects of acute treatment of MK-801 (0.1, 0.2, 0.4 mg/kg) on prepulse inhibition (PPI). (3) To investigate the effects of acute treatment of low-dose MK-801 (0.1 mg/kg) on the object recognition test. Results (1) MK-801 0.2 mg/kg and 0.4 mg/kg increased locomotor activity and decreased PPI in a dose-dependent manner(P<0.05 or 0.01). The 0.1 mg/kg group didn′t show any significant difference in either locomotor activity or PPI compared to the control group.(2) The MK-801 (0.1 mg/kg) group exhibited a significantly lower preference index than the control group in the object recognition test［(57.79±10.66)% vs.（73.34±18.52）%，P<0.05］. Conclusion Medium- and high-dose MK-801 could induce deficits in locomotor activity and sensorimotor gating, whereas low-dose MK-801 could significantly impair the object recognition memory without inducing obvious motor dysfunction, indicating that different doses of MK-801 are recommended when mimicking different endophenotypes of schizophrenia. Key words: Schizophrenia; Dizocilpine maleate; Motor activity; Prepulse inhibition; Object recognition test