Iltis Isabelle, Koski Dee M, Eberly Lynn E, Nelson Christopher D, Deelchand Dinesh K, Valette Julien, Ugurbil Kamil, Lim Kelvin O, Henry Pierre-Gilles
Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, 55455, USA.
NMR Biomed. 2009 Aug;22(7):737-44. doi: 10.1002/nbm.1385.
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 (1)H-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-microL 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.
急性给予苯环己哌啶（PCP）可模拟大鼠精神分裂症的某些方面，如行为改变、多巴胺能活性增加和前额叶皮质功能障碍。在本研究中，我们使用单体素（1）H - MRS来研究急性注射PCP前后大鼠前额叶皮质的神经化学变化。采用短回波时间序列（STEAM）在12只经异氟烷麻醉的大鼠前额叶皮质区域的一个32微升体素中采集光谱。在注射PCP（10 mg/kg，n = 6）或生理盐水（n = 6）的推注前30分钟和推注后140分钟采集数据。代谢物用LCModel进行定量。以10分钟的时间分辨率获得14种代谢物的时间进程。注射PCP后谷氨酰胺/谷氨酸比值显著增加（p < 0.0001，注射前与注射后），而这两种代谢物的总浓度保持不变。注射后葡萄糖短暂增加（+70%），而乳酸减少（两者p < 0.0001）。140分钟后，乳酸恢复到基线水平，但葡萄糖和谷氨酰胺没有。这些结果表明，急性注射PCP会导致谷氨酸和谷氨酰胺浓度发生变化，类似于在精神分裂症患者以及人类给予氯胺酮后所观察到的情况。对这种药理学大鼠模型进行MRS研究可能有助于评估体内潜在抗精神病药物的作用。
