• Masayuki Tomiya, Takeshi Fukushima, Junko Kawai, Chiaki Aoyama, Shogo Mitsuhashi, Tomofumi Santa, Kazuhiro Imai, and Toshimasa Toyo'oka.
• Department of Analytical Chemistry, School of Pharmaceutical Sciences, University of Shizuoka, Japan.
• Biomed. Chromatogr. 2006 Jun 1; 20 (6-7): 628-33.

AbstractIt has been reported that the repeated administration of a sub-anesthetic dose of an N-methyl-D-aspartate receptor antagonist, ketamine, can produce an animal model of schizophrenia. Since no information is available on the alterations of the amino acid levels in ketamine-treated rats, we investigated the amino acid composition in the plasma and cerebrospinal fluid of rats that were repeatedly administered with ketamine for 5 consecutive days (30 mg/kg/day). The plasma and cerebrospinal fluid amino acid compositions in the fifth week after cessation of repeated ketamine administration were determined by highperformance liquid chromatography with fluorescence detection using a pre-column fluorescence reagent, i.e. 4-fluoro-7nitro-2,1,3-benzoxadiazole. Among the amino acids investigated in the present study, the level of plasma glutamic acid increased significantly (p < 0.05), while that of the cerebrospinal fluid glutamic acid decreased significantly in the ketamine-treated rats as compared with these levels in control rats injected with saline (p < 0.05, n = 7). These alterations in the glutamic acid level in the plasma and cerebrospinal fluid resemble those in schizophrenic patients, suggesting that ketamine-treated rats may be a useful model for performing research on the pathophysiology of schizophrenia.Copyright 2006 John Wiley & Sons, Ltd.

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