RESEARCH ARTICLE


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



Tamaki Ishima1, Yuko Fujita1, Mami Kohno1, Shinsui Kunitachi1, Mao Horio1, Yuto Takatsu1, Takahiko Minase1, Yuko Tanibuchi1, 2, Hiroko Hagiwar1, 2, Masaomi Iyo2, Kenji Hashimoto*, 1
1 Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba 260-8670, Japan, and
2 Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan


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© 2009 Ishimaet al;

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba 260-8670, Japan; E-mail: hashimoto@faculty.chiba-u.jp


Abstract

This study was undertaken to examine the effects of the two selective serotonin reuptake inhibitors (SSRIs: fluvoxamine and sertraline) with a high affinity at sigma-1 receptors on cognitive deficits in mice after repeated administration 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.