NEUROCHEMICAL CHANGES IN THE RAT CORTEX IN VIVO LOCALIZED (1)H MRS STUDY

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 急性苯环利定（PCP）给药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。在这项研究中，我们使用单体素1H-MRS研究大鼠前额叶皮层在体内的神经化学变化之前和之后的急性注射PCP。使用短回波时间序列（STEAM）采集异氟烷麻醉的12只大鼠前额叶皮层区域中32-<$L体素的光谱。采集PCP（10 mg/kg，n = 6）或盐水（n = 6）推注前30 min和推注后140 min的数据。用LC模型定量代谢产物。获得了14种代谢物的时间进程，时间分辨率为10 min。注射PCP后谷氨酰胺/谷氨酸盐比值显著增加（p < 0.0001，注射前vs.注射后），而这两种代谢物的总浓度保持不变。注射后葡萄糖短暂升高（+70%），而乳酸降低（均为p < 0.0001）。乳酸盐，但不是葡萄糖和谷氨酰胺，140分钟后恢复到基线水平。这些结果表明，急性注射PCP导致谷氨酸盐和谷氨酰胺浓度的变化，类似于在精神分裂症患者中观察到的，氯胺酮给药后，在人类。这种药理学大鼠模型的MRS研究可能有助于评估潜在的抗精神病药物在体内的作用。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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-¿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.