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.
Neurochem Int. 2011 Dec;59(8):1163-74. doi: 10.1016/j.neuint.2011.10.007. Epub 2011 Oct 25.
The present study was aimed to investigate the behavioral and molecular effects of lamotrigine. To this aim, Wistar rats were treated with lamotrigine (10 and 20 mg/kg) or imipramine (30 mg/kg) acutely and chronically. The behavior was assessed using forced swimming test. Brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), Proteina Kinase B (PKB, AKT), glycogen synthase kinase 3 (GSK-3) and B-cell lymphoma 2 (Bcl-2) levels, citrate synthase, creatine kinase and mitochondrial chain (I, II, II-III and IV) activities were assessed in the brain. The results showed that both treatments reduced the immobility time. The BDNF were increased in the prefrontal after acute treatment with lamotrigine (20 mg/kg), and the BDNF and NGF were increased in the prefrontal after chronic treatment with lamotrigine in all doses. The AKT increased and Bcl-2 and GSK-3 decreased after both treatments in all brain areas. The citrate synthase and creatine kinase increased in the amygdala after acute treatment with imipramine. Chronic treatment with imipramine and lamotrigine (10 mg/kg) increased the creatine kinase in the hippocampus. The complex I was reduced and the complex II, II-III and IV were increased, but related with treatment and brain area. In conclusion, lamotrigine exerted antidepressant-like, which can be attributed to its effects on pathways related to depression, such as neurotrophins, metabolism energy and signaling cascade.
本研究旨在探讨拉莫三嗪的行为和分子效应。为此，将 Wistar 大鼠用拉莫三嗪（10 和 20mg/kg）或丙咪嗪（30mg/kg）急性和慢性处理。使用强迫游泳试验评估行为。在大脑中评估脑源性神经营养因子（BDNF）、神经生长因子（NGF）、蛋白激酶 B（PKB，AKT）、糖原合酶激酶 3（GSK-3）和 B 细胞淋巴瘤 2（Bcl-2）水平、柠檬酸合酶、肌酸激酶和线粒体链（I、II、II-III 和 IV）活性。结果表明，两种处理均减少了不动时间。急性拉莫三嗪（20mg/kg）处理后前额叶 BDNF 增加，所有剂量慢性拉莫三嗪处理后前额叶 BDNF 和 NGF 增加。AKT 在所有脑区增加，Bcl-2 和 GSK-3 在两种处理后减少。急性丙咪嗪处理后杏仁核中柠檬酸合酶和肌酸激酶增加。慢性丙咪嗪和拉莫三嗪（10mg/kg）处理增加了海马中的肌酸激酶。复合物 I 减少，复合物 II、II-III 和 IV 增加，但与处理和脑区有关。总之，拉莫三嗪表现出抗抑郁样作用，这可能归因于其对与抑郁相关的途径的影响，如神经营养因子、代谢能量和信号级联。
