Padilla-de la Torre Mónica, Franco-Pérez Javier, Santamaría Abel, Galvan Sonia, González Edith, Paz Carlos
Departamento de Neurofisiología, Instituto Nacional de Neurología y Neurología, Manuel Velasco Suárez, S.S.A. México, D.F., México.
Ann N Y Acad Sci. 2008 Oct;1139:259-67. doi: 10.1196/annals.1432.038.
Alterations in motor activity related to dopamine changes in some brain regions have been described as consequences of the modifications produced by systemic administration of MK-801 (a noncompetitive NMDA receptor antagonist) in rats. Acetaldehyde (ACH), the main metabolite of ethanol, has been implicated in different alterations in the central nervous system after ethanol ingestion. ACH might exert some control on dopaminergic transmission through the formation of other compounds with dopamine, which eventually may modify dopamine content and its metabolism. In order to evaluate such a hypothesis, we used Wistar rats in the present study to evaluate the effect of ACH on locomotor alterations and dopamine metabolism changes induced by MK-801. Our results show that the MK-801-treated group had a significant increase in locomotor activity. In contrast, we did not find significant differences in locomotion tests after ACH administration. However, the group to which both drugs were administered showed a significant decrease in locomotor activity compared with those given MK-801 alone. Neurochemical analysis showed an increase in dopamine content in the striatum and frontal cortex after MK-801 administration, however; the increase was reversed by giving 200 mg/kg of ACH. These results indicate that ACH can produce an antagonic-like effect on locomotor alterations and dopamine content changes induced by MK-801, thus modulating the MK-801-induced hyperlocomotion by interfering with dopamine metabolism.
在大鼠中，与某些脑区多巴胺变化相关的运动活动改变已被描述为全身给予MK-801（一种非竞争性NMDA受体拮抗剂）所产生的变化的结果。乙醛（ACH）是乙醇的主要代谢产物，在乙醇摄入后中枢神经系统的不同改变中起作用。ACH可能通过与多巴胺形成其他化合物来对多巴胺能传递产生某种控制，最终可能改变多巴胺含量及其代谢。为了评估这一假设，我们在本研究中使用Wistar大鼠来评估ACH对MK-801诱导的运动改变和多巴胺代谢变化的影响。我们的结果表明，MK-801处理组的运动活动显著增加。相比之下，我们在给予ACH后未发现运动测试中有显著差异。然而，与单独给予MK-801的组相比，同时给予两种药物的组的运动活动显著降低。神经化学分析表明，给予MK-801后纹状体和额叶皮质中的多巴胺含量增加；然而，给予200mg/kg的ACH可逆转这种增加。这些结果表明，ACH可对MK-801诱导的运动改变和多巴胺含量变化产生类似拮抗剂的作用，从而通过干扰多巴胺代谢来调节MK-801诱导的运动亢进。
