Department of Pharmacology and Drug Toxicology, Faculty of Pharmacy, Medical University - Plovdiv, "Vassil Aprilov" Blvd. 15A, Plovdiv 4002, Bulgaria.
Department of Anatomy, Histology and Embryology, Faculty of Medicine, Medical University - Plovdiv, "Vassil Aprilov" Blvd. 15A, Plovdiv 4002, Bulgaria.
Pharmacol Biochem Behav. 2018 Jun;169:1-9. doi: 10.1016/j.pbb.2018.03.009. Epub 2018 Mar 29.
Cognitive impairment is considered a frequent side effect in the drug treatment of epilepsy. The objective of the present study was to investigate the effects of lacosamide (LCM) on learning and memory processes in rats, on the serum level of brain-derived neurotrophic factor (BDNF) and BDNF/TrkB ligand receptor system expression in the hippocampal formation. Male Wistar rats underwent long-term treatment with three different doses of lacosamide - 3 mg/kg (LCM 3), 10 mg/kg (LCM 10) and 30 mg/kg (LCM 30). All rats were subjected to one active and one passive avoidance tests. The BDNF/TrkB immunohistochemical expression in the hippocampus was measured and serum BDNF was determined. The LCM-treated rats made fewer avoidance responses than controls during acquisition training and in the memory retention test. The number of escapes in the LCM 10 and LCM 30 groups decreased throughout the test, while the rats in the LCM 3 group showed fewer escapes only in the memory test in the active avoidance task. In the step-down test, the latency time of the LCM-30 treated rats was reduced as compared with the controls during the learning session and the short- and long-term memory retention tests. Lacosamide induced a dose-dependent reduction of the hippocampal expression of BDNF and its receptor TrkB. We found no significant difference between BDNF serum levels in the test animals and controls. The results of the study suggest that LCM suppresses the learning and memory processes in rats, with the inhibition of hippocampal BDNF/TrkB ligand receptor system being one of the possible mechanisms causing this effect.
认知障碍被认为是癫痫药物治疗的常见副作用。本研究的目的是研究拉考酰胺（LCM）对大鼠学习和记忆过程的影响，以及对海马结构中脑源性神经营养因子（BDNF）和 BDNF/TrkB 配体受体系统表达的影响。雄性 Wistar 大鼠接受了三种不同剂量的拉考酰胺长期治疗 - 3mg/kg（LCM 3）、10mg/kg（LCM 10）和 30mg/kg（LCM 30）。所有大鼠都进行了一次主动和一次被动回避测试。测量了海马中的 BDNF/TrkB 免疫组织化学表达，并测定了血清 BDNF。与对照组相比，LCM 治疗组大鼠在获得性训练和记忆保留测试中做出的回避反应更少。LCM 10 组和 LCM 30 组的逃避次数在整个测试过程中减少，而 LCM 3 组的大鼠仅在主动回避任务的记忆测试中表现出较少的逃避。在下台阶测试中，与对照组相比，LCM-30 处理组大鼠在学习阶段以及短期和长期记忆保留测试中的潜伏期时间缩短。拉考酰胺诱导海马 BDNF 及其受体 TrkB 的表达呈剂量依赖性降低。我们发现实验组和对照组之间的血清 BDNF 水平没有显著差异。研究结果表明，LCM 抑制大鼠的学习和记忆过程，而抑制海马 BDNF/TrkB 配体受体系统是引起这种效应的可能机制之一。
