Ketamine is a noncompetitive antagonist of glutamatergic N-methyl-d-aspartate receptors. Its acute effects on healthy volunteers and schizophrenia patients mimic some acute psychotic, but also cognitive and negative symptoms of schizophrenia, and subchronic treatment with ketamine has been used as an animal model of psychotic disorders. Glutamatergic neurotransmission is tightly coupled to oxidative metabolism in the brain. Quantitative histochemical mapping of cytochrome c oxidase (COX) activity, which reflect long-term energy metabolism, was carried out in rats that received a daily subanaesthetic dose (30 mg/kg) of ketamine for 10 days. In total, COX activity was measured in 190 brain regions to map out metabolic adaptations to the subchronic administration of ketamine. Ketamine treatment was associated with elevated COX activity in nine brain sub-regions in sensory thalamus, basal ganglia, cortical areas, hippocampus and superior colliculi. Changes in pairwise correlations between brain regions were studied with differential correlation analysis. Ketamine treatment was associated with the reduction of positive association between brain regions in 66 % of the significant comparisons. Different layers of the superior colliculi showed the strongest effects. Changes in other visual and auditory brain centres were also of note. The locus coeruleus showed opposite pattern of increased coupling to mainly limbic brain regions in ketamine-treated rats. Our study replicated commonly observed activating effects of ketamine in the hippocampus, cingulate cortex, and basal ganglia. The current study is the first to extensively map the oxidative metabolism in the CNS in the ketamine model of schizophrenia. It shows that ketamine treatment leads to the re-organization of activity in sensory and memory-related brain circuits.

氯胺酮是谷氨酸能N-甲基-d的非竞争性拮抗剂-天冬氨酸受体。它对健康志愿者和精神分裂症患者的急性作用模仿了一些急性精神病，但也模仿了精神分裂症的认知和阴性症状，氯胺酮的亚慢性治疗已被用作精神病的动物模型。谷氨酸能神经传递与大脑中的氧化代谢紧密相关。在每天接受亚麻醉剂量（30 mg / kg）的氯胺酮治疗10天的大鼠中，进行了反映长期能量代谢的细胞色素c氧化酶（COX）活性的定量组织化学标测。总体而言，在190个大脑区域中测量了COX活性，以绘制出与氯胺酮亚慢性给药有关的代谢适应情况。氯胺酮治疗与感觉丘脑，基底神经节，皮层区，海马和上丘。用微分相关分析研究了大脑区域之间成对相关的变化。氯胺酮治疗与大脑区域之间正相关的减少有66％的显着比较。上丘胶的不同层显示最强的作用。其他视觉和听觉大脑中枢的变化也值得注意。在氯胺酮治疗的大鼠中，脑蓝斑显示出与主要边缘脑区的偶联增加的相反模式。我们的研究复制了氯胺酮在海马，扣带回皮层和基底神经节中通常观察到的激活作用。当前的研究是第一个广泛绘制精神分裂症氯胺酮模型中中枢神经系统氧化代谢的图谱。