Osorio-Rico Laura, Mancera-Flores Mayra, Ríos Camilo
Department of Neurochemistry, National Institute of Neurology and Neurosurgery, México.
Pharmacol Toxicol. 2003 Mar;92(3):143-7. doi: 10.1034/j.1600-0773.2003.920307.x.
Kainic acid induces seizures and neurotoxicity in rats, produces changes in brain serotonin (5-HT), dopamine and noradrenaline metabolites among other changes in neurotransmitters. In this work, we investigated the changes in 5-HT turnover in brain regions from 84 rats intraperitoneally injected with kainic acid and a specific behavioural change, the body and head shakes, exerted by this neurotoxin in the presence of 5-HT receptor antagonists. Kainic acid produced an increase in 5-hydroxyindoleacetic acid levels in frontal cortex (212%; 180%), striatum (177%; 116%), amygdala (202%; 337%) and hippocampus (43%; 70 %) at 2 and 24 hr as compared with controls, respectively. Serotonin turnover was increased in amygdala (157%) and frontal cortex (169%) at 2 hr; whereas 24 hr after kainic acid administration, increases were observed in amygdala (207%), and frontal cortex (178%). Kainic acid also produced an increase in the frequency of head and body shakes when administered alone or together with pargyline, a monoamine oxidase inhibitor; whereas the administration of 5-HT receptor antagonists such as ketanserin and methiothepin, decreased this behaviour 54% and 50% as compared with kainic acid alone, respectively. These results suggest an active participation of 5-HT neurotransmission on the excitotoxic action of kainic acid in the brain.
海藻酸可诱导大鼠癫痫发作和神经毒性,导致大脑中血清素(5-羟色胺,5-HT)、多巴胺和去甲肾上腺素代谢产物发生变化,以及神经递质出现其他改变。在本研究中,我们调查了84只腹腔注射海藻酸的大鼠脑区中5-HT周转率的变化,以及在5-HT受体拮抗剂存在的情况下,这种神经毒素所引发的一种特定行为变化,即身体和头部震颤。与对照组相比,海藻酸在2小时和24小时时分别使额叶皮质(212%;180%)、纹状体(177%;116%)、杏仁核(202%;337%)和海马体(43%;70%)中的5-羟吲哚乙酸水平升高。2小时时,杏仁核(157%)和额叶皮质(169%)中的血清素周转率增加;而在给予海藻酸24小时后,杏仁核(207%)和额叶皮质(178%)出现增加。单独给予海藻酸或与单胺氧化酶抑制剂帕吉林一起给予时,海藻酸还会增加头部和身体震颤的频率;而给予5-HT受体拮抗剂如酮色林和甲硫噻平,与单独给予海藻酸相比,这种行为分别减少了54%和50%。这些结果表明5-HT神经传递积极参与了海藻酸在大脑中的兴奋性毒性作用。