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

• Published in: The open clinical chemistry journal Vol. 2; no. 1; pp. 7 - 11
• Main Authors: Ishima, Tamaki, Fujita, Yuko, Kohno, Mami, Kunitachi, Shinsui, Horio, Mao, Takatsu, Yuto, Minase, Takahiko, Tanibuchi, Yuko, Hagiwar, Hiroko, Iyo, Masaomi, Hashimoto, Kenji
• Format: Journal Article
• Language: English
• Published: 01.01.2009
• ISSN: 1874-2416; 1874-2416
• DOI: 10.2174/1874241600902010007

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.