Laboratório de Neurociências and Instituto Nacional de Ciência e Tecnologia Translacional em Medicina, Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, 88806-000 Criciúma, SC, Brazil.
Brain Res Bull. 2010 Apr 5;81(6):585-9. doi: 10.1016/j.brainresbull.2009.11.013. Epub 2009 Nov 30.
A growing body of evidence has pointed to the NMDA receptor antagonists as a potential therapeutic target for the treatment of major depression. The present study was aimed to evaluate behavioural and molecular effects of the acute and chronic treatment with memantine and imipramine in rats. To this aim, rats were acutely or chronically for 14 days once a day treated with memantine (5, 10 and 20 mg/kg) and imipramine (10, 20 and 30 mg/kg) and then subjected to the forced swimming and open-field tests. The acute treatment with memantine at all doses and imipramine at doses (20 and 30 mg/kg) reduced immobility time of rats compared to the saline group (p < 0.05), without affecting spontaneous locomotor activity and chronic treatment with memantine and imipramine, at all doses tested, reduced immobility time of rats compared to the saline group (p < 0.05), without affecting spontaneous locomotor activity. Brain-derived neurotrophic factor (BDNF) hippocampal levels were assessed in imipramine- and memantine-treated rats by ELISA sandwich assay. Interesting enough, acute administration, but not chronic administration of memantine at higher dose (20 mg/kg) increased BDNF protein levels in the rat hippocampus (p < 0.05). Finally, these findings further support the hypothesis that NMDA receptor could be a new pharmacological target for the treatment of depression.
越来越多的证据表明，NMDA 受体拮抗剂可能成为治疗重度抑郁症的潜在治疗靶点。本研究旨在评估美金刚和丙咪嗪在大鼠中的急性和慢性治疗的行为和分子效应。为此，大鼠每天接受一次急性或慢性治疗，持续 14 天，美金刚（5、10 和 20mg/kg）和丙咪嗪（10、20 和 30mg/kg），然后进行强迫游泳和旷场试验。与生理盐水组相比，所有剂量的美金刚和 20 和 30mg/kg 的丙咪嗪急性治疗均可降低大鼠的不动时间（p<0.05），而不影响自发运动活动；所有测试剂量的美金刚和丙咪嗪慢性治疗均可降低大鼠的不动时间与生理盐水组相比（p<0.05），而不影响自发运动活动。通过 ELISA 夹心测定法评估了丙咪嗪和美金刚治疗大鼠的海马脑源性神经营养因子（BDNF）水平。有趣的是，急性给药而非慢性给药较高剂量（20mg/kg）的美金刚可增加大鼠海马中的 BDNF 蛋白水平（p<0.05）。最后，这些发现进一步支持了 NMDA 受体可能成为治疗抑郁症的新药理学靶点的假设。
