Neurochemical changes in the rat prefrontal cortex following acute phencyclidine treatment: an in vivo localized 1H MRS study
Neurochemical changes in the rat prefrontal cortex following acute phencyclidine treatment: an in vivo localized 1H MRS study
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DOI：
10.1002/nbm.1385
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发表时间：
2009-08-01
影响因子：
2.9
通讯作者：
Henry, Pierre-Gilles
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文献类型：
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作者：
Iltis, Isabelle;Koski, Dee M.;Henry, Pierre-Gilles
急性苯环己哌啶（PCP）给药模拟了大鼠精神分裂症的某些方面，例如行为改变、多巴胺能活性增加和前额皮质功能障碍。在本研究中，我们使用单体素 H-1-MRS 来研究急性注射 PCP 前后大鼠前额皮质体内神经化学变化。使用短回波时间序列 (STEAM) 获取位于异氟烷麻醉的 12 只大鼠前额皮质区域的 32 μL 体素的光谱。在推注 PCP（10 mg/kg，n = 6）或盐水（n = 6）之前 30 分钟和之后 140 分钟获取数据。使用 LCModel 对代谢物进行定量。获得 14 种代谢物的时间进程，时间分辨率为 10 分钟。 PCP 注射后谷氨酰胺/谷氨酸比率显着增加（注射前与注射后相比，p < 0.0001），而这两种代谢物的总浓度保持恒定。注射后血糖短暂升高 (+70%)，而乳酸降低（均 p < 0.0001）。 140 分钟后，乳酸（而非葡萄糖和谷氨酰胺）恢复到基线水平。这些结果表明，急性注射五氯苯酚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中以及在人类服用氯胺酮后观察到的情况。这种药理学大鼠模型的 MRS 研究可能有助于评估潜在抗精神病药物的体内作用。版权所有 (C) 2009 John Wiley & Sons, Ltd.
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 H-1-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-mu L 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 (C) 2009 John Wiley & Sons, Ltd.