PMID- 29605232 OWN - NLM STAT- MEDLINE DCOM- 20190315 LR - 20200930 IS - 1873-5177 (Electronic) IS - 0091-3057 (Linking) VI - 169 DP - 2018 Jun TI - Chronic treatment with the new anticonvulsant drug lacosamide impairs learning and memory processes in rats: A possible role of BDNF/TrkB ligand receptor system. PG - 1-9 LID - S0091-3057(17)30698-6 [pii] LID - 10.1016/j.pbb.2018.03.009 [doi] AB - 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. CI - Copyright (c) 2018 Elsevier Inc. All rights reserved. FAU - Shishmanova-Doseva, Michaela AU - Shishmanova-Doseva M AD - Department of Pharmacology and Drug Toxicology, Faculty of Pharmacy, Medical University - Plovdiv, "Vassil Aprilov" Blvd. 15A, Plovdiv 4002, Bulgaria. Electronic address: shishmanovamichaella@gmail.com. FAU - Peychev, Lyudmil AU - Peychev L AD - Department of Pharmacology and Drug Toxicology, Faculty of Pharmacy, Medical University - Plovdiv, "Vassil Aprilov" Blvd. 15A, Plovdiv 4002, Bulgaria. Electronic address: peych@propolisbg.com. FAU - Koeva, Yvetta AU - Koeva Y AD - Department of Anatomy, Histology and Embryology, Faculty of Medicine, Medical University - Plovdiv, "Vassil Aprilov" Blvd. 15A, Plovdiv 4002, Bulgaria. Electronic address: yvetta_k@abv.bg. FAU - Terzieva, Dora AU - Terzieva D AD - Department of Clinical Laboratory, Faculty of Pharmacy, Medical University - Plovdiv, "Vassil Aprilov" Blvd. 15A, Plovdiv 4002, Bulgaria. Electronic address: terzieva2006@yahoo.com. FAU - Georgieva, Katerina AU - Georgieva K AD - Department of Physiology, Faculty of Medicine, Medical University - Plovdiv, "Vassil Aprilov" Blvd. 15A, Plovdiv 4002, Bulgaria. Electronic address: kng@plov.net. FAU - Peychev, Zhivko AU - Peychev Z AD - Department of Medical Informatics, Biostatistics and E-learning, Faculty of Public Health, Medical University-Plovdiv, "Vassil Aprilov" Blvd. 15A, Plovdiv 4002, Bulgaria. Electronic address: zhpeychev@meduniversity-plovdiv.bg. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180329 PL - United States TA - Pharmacol Biochem Behav JT - Pharmacology, biochemistry, and behavior JID - 0367050 RN - 0 (Anticonvulsants) RN - 0 (Bdnf protein, rat) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 563KS2PQY5 (Lacosamide) RN - EC 2.7.10.1 (Ntrk2 protein, rat) RN - EC 2.7.10.1 (Receptor, trkB) SB - IM MH - Animals MH - Anticonvulsants/administration & dosage/*pharmacology MH - Brain-Derived Neurotrophic Factor/blood/*metabolism MH - Dose-Response Relationship, Drug MH - Hippocampus/drug effects/metabolism MH - Immunohistochemistry MH - Lacosamide/administration & dosage/*pharmacology MH - Learning/*drug effects MH - Male MH - Memory/*drug effects MH - Rats, Wistar MH - Reaction Time/drug effects MH - Receptor, trkB/blood/*metabolism OTO - NOTNLM OT - Antiepileptic drugs OT - BDNF OT - Cognitive function OT - Lacosamide OT - Rats OT - TrkB EDAT- 2018/04/02 06:00 MHDA- 2019/03/16 06:00 CRDT- 2018/04/02 06:00 PHST- 2017/12/10 00:00 [received] PHST- 2018/03/23 00:00 [revised] PHST- 2018/03/26 00:00 [accepted] PHST- 2018/04/02 06:00 [pubmed] PHST- 2019/03/16 06:00 [medline] PHST- 2018/04/02 06:00 [entrez] AID - S0091-3057(17)30698-6 [pii] AID - 10.1016/j.pbb.2018.03.009 [doi] PST - ppublish SO - Pharmacol Biochem Behav. 2018 Jun;169:1-9. doi: 10.1016/j.pbb.2018.03.009. Epub 2018 Mar 29.