Neurochemical changes in the rat prefrontal cortex following acute phencyclidine treatment: an in vivo localized 1H MRS study

NMR in Biomedicine - Tập 22 Số 7 - Trang 737-744 - 2009
Isabelle Iltis1, Dee M. Koski1, Lynn E. Eberly2, Christopher D. Nelson1, Dinesh K. Deelchand1, Julien Valette1, Kâmil Uǧurbil1, Kelvin O. Lim1,3,4, Pierre‐Gilles Henry1
1Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN, USA
2Division of Biostatistics, School of Public Health, 420 Delaware Street SE, University of Minnesota, Minneapolis, MN, USA
3Department of Psychiatry, University of Minnesota, Minneapolis, MN USA
4Geriatric Research, Education, and Clinical Center, Veterans Affairs Medical Center, Minneapolis, MN, USA

Tóm tắt

Abstract

Acute phencyclidine (PCP) administration mimics some aspects of schizophrenia in rats, such as behavioral alterations, increased dopaminergic activity and prefrontal cortex dysfunction. In this study, we used single‐voxel 1H‐MRS to investigate neurochemical changes in rat prefrontal cortex in vivo before and after an acute injection of PCP. A short‐echo time sequence (STEAM) was used to acquire spectra in a 32‐µL voxel positioned in the prefrontal cortex area of 12 rats anesthetized with isoflurane. Data were acquired for 30 min before and for 140 min after a bolus of PCP (10 mg/kg, n = 6) or saline (n = 6). Metabolites were quantified with the LCModel. Time courses for 14 metabolites were obtained with a temporal resolution of 10 min. The glutamine/glutamate ratio was significantly increased after PCP injection (p < 0.0001, pre‐ vs. post‐injection), while the total concentration of these two metabolites remained constant. Glucose was transiently increased (+70%) while lactate decreased after the injection (both p < 0.0001). Lactate, but not glucose and glutamine, returned to baseline levels after 140 min. These results show that an acute injection of PCP leads to changes in glutamate and glutamine concentrations, similar to what has been observed in schizophrenic patients, and after ketamine administration in humans. MRS studies of this pharmacological rat model may be useful for assessing the effects of potential anti‐psychotic drugs in vivo. Copyright © 2009 John Wiley & Sons, Ltd.

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NMR in Biomedicine

Tập 22 Số 7

737-744

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