【文题】Repeated application of ketamine to rats induces changes in the hippocampal expression of parvalbumin, neuronal nitric oxide synthase and cFOS similar to those found in human schizophrenia.
【杂志】Neuroscience. 2004;126(3):591-8
【作者】Keilhoff G, Becker A, Grecksch G, Wolf G, Bernstein HG.
【单位】Institute of Medical Neurobiology, University of Magdeburg, Leipziger Strasse 44, D-39120 Magdeburg, Germany. gerburg.keilhoff@medizin.uni-magdeburg.de

【文摘】Treatment with the phencyclidine derivative ketamine, a non-competitive N-methyl-D-aspartate receptor antagonist and a well known anesthetic, has recently been introduced to mimic schizophrenia in animals. Using rats repeatedly treated with sub-anesthetic doses we demonstrate in the hippocampal formation the cellular distribution patterns of proteins being relevant to the pathogenesis of schizophrenia. Compared with controls an increase in the density of reduced nicotinamide adenine dinucleotide phosphate diaphorase-, neuronal nitric oxide synthase- and cFOS-positive hippocampal interneurons was found, whereas the density of parvalbumin expressing cells was decreased. Our experiments show that repeated injections of sub-anesthetic doses of ketamine induce significant changes in the nitrergic and GABAergic system which, in part, resemble those described in postmortem brains of human schizophrenics indicating that sub-chronic treatment with sub-anesthetic doses of ketamine might be a useful animal model to study schizophrenia.

【翻译】最近研究表明苯环己哌啶的衍生物氯胺酮（一种非竞争性N-甲基-D-天冬氨酸受体拮抗剂，常见的麻醉剂）能诱导动物产生精神分裂症样症状。我们采用亚麻醉剂量氯胺酮反复给药的方式以研究与精神分裂症发病机制相关的大鼠海马细胞中蛋白分布形式的变化。与对照组相比实验组还原型烟酰胺腺嘌呤磷酸二核苷酸、神经型一氧化氮合酶和cFOS阳性的海马中间神经元密度增加，而表达微白蛋白的细胞密度下降。我们的研究表明重复给予亚麻醉剂量的氯胺酮能明显改变硝基能和GABA能系统，这与人类精神分裂症患者脑尸检结果部分上相似。提示反复给予亚麻醉剂量的氯胺酮可能是研究精神分裂症有用的动物模型。

转自  ziyu00