Metabolic mapping of the rat brain after subanesthetic doses of ketamine: potential relevance to schizophrenia
Metabolic mapping of the rat brain after subanesthetic doses of ketamine: potential relevance to schizophrenia
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DOI：
10.1016/s0006-8993(97)01390-5
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发表时间：
1998-03-23
期刊：
影响因子：
2.9
通讯作者：
Breese, GR
中科院分区：
文献类型：
--
作者：
Duncan, GE;Moy, SS;Breese, GR
亚麻醉剂量的氯胺酮已被证明会加重精神分裂症的症状，并在正常受试者中诱导阳性、阴性和认知性精神分裂症样症状。本研究旨在确定受亚麻醉剂量氯胺酮影响的脑区，使用C-14-2-脱氧葡萄糖（2-DG）摄取的高分辨率放射自显影分析和Fos样免疫反应性（Fos-LI）的免疫细胞化学染色。这两种功能定位方法都被使用，因为这两种定位方法通常可以获得不同和互补的信息。氯胺酮，在亚麻醉剂量为35毫克/公斤，大幅增加2-DG摄取在某些边缘皮质区，包括内侧前额叶，腹外侧眶，扣带，和压后皮质。在海马结构中，亚麻醉剂量的氯胺酮诱导齿状回、CA-3放射层、分子陷窝层和前下托的2-DG摄取显著增加。在选择的丘脑核和基底外侧杏仁核中也观察到对35 mg/kg氯胺酮的响应增加的2-DG摄取。氯胺酮诱导Fos-LI在相同的边缘皮质区域，表现出增加2-DG摄取的亚麻醉剂量的药物。然而，没有诱导Fos在一些大脑区域，显示增加2-DG摄取，如海马结构，前腹侧丘脑核，基底外侧杏仁核。相反，氯胺酮诱导的Fos下丘脑室旁核和中央杏仁核，虽然没有影响的药物2-DG摄取是明显的，在这些地区。与亚麻醉剂量后在选定脑区观察到的2-DG摄取增加相反，麻醉剂量的氯胺酮（100 mg/kg）对2-DG摄取产生了全面抑制。相比之下，在麻醉剂量的氯胺酮后观察到Fos-LI的稳健诱导，其在神经解剖学上与亚麻醉剂量产生的诱导相同。本研究的结果表明，麻醉和亚麻醉剂量的氯胺酮对局部脑2-DG摄取和诱导Fos-LI有显着的影响。亚麻醉剂量引起的局部脑代谢的改变可能与氯胺酮诱导精神分裂症样症状的作用有关。(C)1998年Elsevier Science B.V.
Subanesthetic doses of ketamine have been shown to exacerbate symptoms in schizophrenia and to induce positive, negative, and cognitive schizophrenic-like symptoms in normal subjects. The present investigation sought to define brain regions affected by subanesthetic doses of ketamine, using high resolution autoradiographic analysis of C-14-2-deoxyglucose (2-DG) uptake and immunocytochemical staining for Fos-like immunoreactivity (Fos-LI). Both functional mapping approaches were used because distinct and complementary information is often obtained with these two mapping methods. Ketamine, at a subanesthetic dose of 35 mg/kg, substantially increased 2-DG uptake in certain limbic cortical regions, including medial prefrontal, ventrolateral orbital, cingulate, and retrosplenial cortices. In the hippocampal formation, the subanesthetic dose of ketamine induced prominent increases in 2-DG uptake in the dentate gyrus, CA-3 stratum radiatum, stratum lacunosum moleculare, and presubiculum. Increased 2-DG uptake in response to 35 mg/kg ketamine was also observed in select thalamic nuclei and basolateral amygdala. Ketamine induced Fos-LI in the same limbic cortical regions that exhibited increased 2-DG uptake in response to the subanesthetic dose of the drug. However, no Fos was induced in some brain regions that showed increased 2-DG uptake, such as the hippocampal formation, anterioventral thalamic nucleus, and basolateral amygdala. Conversely, ketamine induced Fos in the paraventricular nucleus of the hypothalamus and central amygdala, although no effect of the drug on 2-DG uptake was apparent in these regions. In contrast to the increase in 2-DG uptake observed in select brain regions after the subanesthetic dose, an anesthetic dose of ketamine (100 mg/kg) produced a global suppression of 2-DG uptake. By contrast, a robust induction of Fos-LI was observed after the anesthetic dose of ketamine that was neuroanatomically identical to that produced by the subanesthetic dose. Results of the present investigation show that anesthetic and subanesthetic doses of ketamine have pronounced effects on regional brain 2-DG uptake and induction of Fos-LI. The alterations in regional brain metabolism induced by the subanesthetic dose may be relevant to effects of ketamine to induce schizophrenic-like symptoms. (C) 1998 Elsevier Science B.V.