Improvement of Phencyclidine-Induced Cognitive Deficits in Mice by Subsequent Subchronic Administration of Fluvoxamine, but not Sertraline

Abstract

This study was undertaken to examine the effects of the two selective serotonin reuptake inhibitors (SSRIs: flu- voxamine and sertraline) with a high affinity at sigma-1 receptors on cognitive deficits in mice after repeated administra- tion of the N-methyl-D-asparatte (NMDA) receptor antagonist phencyclidine (PCP). In the novel object recognition test (NORT), PCP (10 mg/kg/day, 10 days)-induced cognitive deficits in mice were significantly improved by subsequent subchronic (14 days) administration of fluvoxamine (20 mg/kg/day), but not sertraline (10 or 20 mg/kg/day). Western blot analysis revealed that repeated administration of PCP (10 mg/kg/day, 10 days) caused the reduction of sigma-1 receptors in the frontal cortex and hippocampus of mouse brain. These findings suggest that repeated administration of PCP caused the reduction of sigma-1 receptors in the mouse brain, and that sigma-1 receptor agonists such as fluvoxamine may be useful for treatment of cognitive deficits in schizophrenia.