In vivo and ex vivo evidence for ketamine-induced hyperglutamatergic activity in the cerebral cortex of the rat: Potential relevance to schizophrenia

Authors

  • Sang-Young Kim,

    1. Department of Biomedical Engineering, College of Medicine, The Catholic University of Korea, Seoul, Korea
    2. Research Institute of Biomedical Engineering, The Catholic University of Korea, Seoul, Korea
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  • Hyunseung Lee,

    1. Division of Magnetic Resonance Research, Korea Basic Science Institute, Choongbuk, Korea
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  • Hyun-Ju Kim,

    1. Seoul Center, Korea Basic Science Institute, Seoul, Korea
    2. Department of Biotechnology, School of Life Science & Biotechnology, Korea University, Seoul, Korea
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  • Eunjung Bang,

    1. Seoul Center, Korea Basic Science Institute, Seoul, Korea
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  • Sung-Ho Lee,

    1. Department of Veterinary Surgery, College of Veterinary Medicine, Konkuk University, Seoul, Korea
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  • Do-Wan Lee,

    1. Department of Biomedical Engineering, College of Medicine, The Catholic University of Korea, Seoul, Korea
    2. Research Institute of Biomedical Engineering, The Catholic University of Korea, Seoul, Korea
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  • Dong-Cheol Woo,

    1. Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
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  • Chi-Bong Choi,

    1. Department of Veterinary Diagnostic Radiology, Dr. PET Animal Medical Center, 35-3 Samsung-Dong, Kangnam-Gu, Seoul, Korea, 135-867
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  • Kwan Soo Hong,

    1. Division of Magnetic Resonance Research, Korea Basic Science Institute, Choongbuk, Korea
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  • Chulhyun Lee,

    1. Division of Magnetic Resonance Research, Korea Basic Science Institute, Choongbuk, Korea
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  • Bo-Young Choe

    Corresponding author
    1. Department of Biomedical Engineering, College of Medicine, The Catholic University of Korea, Seoul, Korea
    2. Research Institute of Biomedical Engineering, The Catholic University of Korea, Seoul, Korea
    • Department of Biomedical Engineering, College of Medicine, The Catholic University of Korea, no. 505 Banpo-Dong, Seocho-Gu, Seoul 137-040, Republic of Korea

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  • This paper was presented at The 18th Scientific Meeting and Exhibition of the International Society of Magnetic Resonance in Medicine at Stockholm, Sweden, 1–7 May 2010.

Abstract

Subanesthetic doses of ketamine, a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, impair prefrontal cortex (PFC) function in the rat and produce symptoms in humans similar to those observed in patients with schizophrenia. In the present study, in vivo 1H-MRS and ex vivo 1H high-resolution magic angle spinning (HR-MAS) spectroscopy was used to examine the brain metabolism of rats treated with subanesthetic doses of ketamine (30 mg/kg) for 6 days. A single voxel localization sequence (PRESS, TR/TE = 4000/20 ms and NEX = 512) was used to acquire the spectra in a 30-µl voxel positioned in the cerebral cortex (including mainly PFC) of the rats (ketamine group: n = 12; saline group: n = 12) anesthetized with isoflurane. After the in vivo 1H-MRS acquisition, the animals were sacrificed and the cerebral cortex tissues were extracted (ketamine group: n = 7; saline group: n = 7) for ex vivo 1H HR-MAS spectroscopy (CPMG sequence, 2.0-s presaturation delay, 2.0-s acquisition time, 128 transients and 4-ms inter-pulse delay) using a 500-MHz NMR spectrometer. All proton metabolites were quantified using the LCModel. For the in vivo spectra, there was a significant increase in glutamate concentration in the cerebral cortex of the ketamine group compared with the controls (p < 0.05). For the ex vivo HR-MAS spectra, there was a significant increase in the glutamate/total creatine ratio, and a decrease in the glutamine/total creatine and glutamine/glutamate ratios in the cerebral cortex tissue of the ketamine group compared with the controls. The results of the present study demonstrated that administration of subanesthetic doses of ketamine in the rat may exert at least part of their effect in the cerebral cortex by activation of glutamatergic neurotransmission. Copyright © 2011 John Wiley & Sons, Ltd.

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