Tomiya Masayuki, Fukushima Takeshi, Kawai Junko, Aoyama Chiaki, Mitsuhashi Shogo, Santa Tomofumi, Imai Kazuhiro, Toyo'oka Toshimasa
Department of Analytical Chemistry, School of Pharmaceutical Sciences, University of Shizuoka, Japan.
Biomed Chromatogr. 2006 Jun-Jul;20(6-7):628-33. doi: 10.1002/bmc.677.
It has been reported that the repeated administration of a sub-anesthetic dose of an N-methyl-D-aspartate receptor antagonist, ketamine, can produce an animal model of schizophrenia. Since no information is available on the alterations of the amino acid levels in ketamine-treated rats, we investigated the amino acid composition in the plasma and cerebrospinal fluid of rats that were repeatedly administered with ketamine for 5 consecutive days (30 mg/kg/day). The plasma and cerebrospinal fluid amino acid compositions in the fifth week after cessation of repeated ketamine administration were determined by highperformance liquid chromatography with fluorescence detection using a pre-column fluorescence reagent, i.e. 4-fluoro-7nitro-2,1,3-benzoxadiazole. Among the amino acids investigated in the present study, the level of plasma glutamic acid increased significantly (p < 0.05), while that of the cerebrospinal fluid glutamic acid decreased significantly in the ketamine-treated rats as compared with these levels in control rats injected with saline (p < 0.05, n = 7). These alterations in the glutamic acid level in the plasma and cerebrospinal fluid resemble those in schizophrenic patients, suggesting that ketamine-treated rats may be a useful model for performing research on the pathophysiology of schizophrenia.
据报道，重复给予亚麻醉剂量的N-甲基-D-天冬氨酸受体拮抗剂氯胺酮可产生精神分裂症动物模型。由于目前尚无关于氯胺酮处理大鼠氨基酸水平变化的信息，我们研究了连续5天（30毫克/千克/天）重复给予氯胺酮的大鼠血浆和脑脊液中的氨基酸组成。在重复给予氯胺酮停止后的第五周，使用柱前荧光试剂4-氟-7-硝基-2,1,3-苯并恶二唑，通过高效液相色谱荧光检测法测定血浆和脑脊液中的氨基酸组成。在本研究中所检测的氨基酸中，与注射生理盐水的对照大鼠相比，氯胺酮处理大鼠的血浆谷氨酸水平显著升高（p<0.05），而脑脊液谷氨酸水平则显著降低（p<0.05，n = 7）。血浆和脑脊液中谷氨酸水平的这些变化与精神分裂症患者的情况相似，这表明氯胺酮处理的大鼠可能是用于精神分裂症病理生理学研究的有用模型。
