Uomoto M, Nishibori M, Nakaya N, Takeuchi Y, Iwagaki H, Tanaka N, Saeki K
Department of Pharmacology, Okayama University Medical School, Japan.
J Neurochem. 1998 Jan;70(1):260-7. doi: 10.1046/j.1471-4159.1998.70010260.x.
Patients with cancer cachexia often suffer from psychiatric disorders. In the present study, we investigated the changes in monoaminergic activities in the brain in tumor-bearing mice with reference to the development of cachexia. Two clones, clone-5 (noncachectic clone) and clone-20 (cachectic clone), derived from the murine Colon-26 adenocarcinoma cell line (Nippon Roche Research Center), were inoculated subcutaneously at 1 x 10(6) cells/0.2 ml into the right lower back of BALB/c mice. In clone-20 mice, body weight and locomotor activity decreased significantly 10-15 days after tumor inoculation. The levels of noradrenaline, dopamine, and 3,4-dihydroxyphenylacetic acid showed no significant change among the three groups. The noradrenaline turnover rate in clone-20 mice was increased in cerebral cortex, hypothalamus, and midbrain. The 5-hydroxytryptamine turnover rate in clone-20 mice was increased in hippocampus, cerebral cortex, midbrain, and pons-medulla oblongata. In contrast, the dopamine turnover rate in clone-20 mice was decreased markedly in hippocampus, cerebral cortex, striatum, hypothalamus, and cerebellum. There was no significant change in amine turnover between control and clone-5 mice except for dopamine in hippocampus, cerebral cortex, and striatum and 5-hydroxytryptamine in striatum. No significant change in the levels of amino acids in the brain was observed among the three groups of mice. It is concluded that some of the psychiatric disorders from which cancer cachectic patients suffer might be ascribable to changes in monoaminergic activities in the brain.
癌症恶病质患者常伴有精神障碍。在本研究中,我们参照恶病质的发展情况,调查了荷瘤小鼠大脑中单胺能活性的变化。从鼠结肠26腺癌细胞系(日本罗氏研究中心)获得的两个克隆,克隆-5(非恶病质克隆)和克隆-20(恶病质克隆),以1×10(6) 个细胞/0.2 ml的剂量皮下接种到BALB/c小鼠的右下背部。在克隆-20小鼠中,接种肿瘤后10 - 15天体重和运动活性显著下降。三组中去甲肾上腺素、多巴胺和3,4-二羟基苯乙酸的水平无显著变化。克隆-20小鼠大脑皮质、下丘脑和中脑的去甲肾上腺素周转率增加。克隆-20小鼠海马、大脑皮质、中脑和脑桥-延髓的5-羟色胺周转率增加。相反,克隆-20小鼠海马、大脑皮质、纹状体、下丘脑和小脑的多巴胺周转率显著降低。除海马、大脑皮质和纹状体中的多巴胺以及纹状体中的5-羟色胺外,对照小鼠和克隆-5小鼠之间的胺周转率无显著变化。三组小鼠大脑中的氨基酸水平无显著变化。结论是,癌症恶病质患者所患的一些精神障碍可能归因于大脑中单胺能活性的变化。