The effect of acetylcholinesterase inhibitor rivastigmine in pentylenetetrazole-induced kindling model of epilepsy in rats.

Autor: Ak ET; Department of Physiology, Medical School, University of Ondokuz Mayis, Samsun, 55139, Türkiye., Okuyucu B; Department of Physiology, Medical School, University of Ondokuz Mayis, Samsun, 55139, Türkiye., Hatipoğlu B; Department of Physiology, Medical School, University of Ondokuz Mayis, Samsun, 55139, Türkiye., Arslan G; Department of Physiology, Medical School, University of Ondokuz Mayis, Samsun, 55139, Türkiye. gokhan.arslan@omu.edu.tr.
Jazyk: angličtina
Zdroj: Naunyn-Schmiedeberg's archives of pharmacology [Naunyn Schmiedebergs Arch Pharmacol] 2024 Dec 07. Date of Electronic Publication: 2024 Dec 07.
DOI: 10.1007/s00210-024-03679-3
Abstrakt: This study aimed to investigate the role of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitor rivastigmine (RIVA) in the pentylenetetrazole (PTZ)- induced kindling model of epilepsy. The current study consists of three steps; 1) Saline or RIVA (0.5, 1, and 2 mg/kg) was administered intraperitoneally (i.p.) 15 min before PTZ (35 mg/kg) during the kindling process and seizure behaviors were observed; 2) Single doses of RIVA (0.25, 0.5, and 1 mg/kg; i.p.) was administered to the electrode implanted kindled rats 15 min before PTZ and electrocorticogram (ECoG) recordings were obtained; 3) Low-dose of RIVA (0.5 mg/kg) was administered to the kindled rats for 14 consecutive days and after 24 h PTZ was administered and ECoG recordings were obtained. In addition, 24 h after the PTZ injection, the hippocampus was extracted and mRNA expression levels of N-methyl D-aspartate receptor subunit 2B (NR2B) and brain-derived neurotrophic factor (BDNF) were measured by qPCR analysis. Only low-dose of RIVA increased resistance against kindling. Single and long-term administration of low-dose RIVA increased the latency to the first myoclonic jerk, decreased the duration of generalized tonic-clonic seizures, and reduced the seizure stage in kindled rats. Long-term low-dose RIVA treatment decreased the mRNA expressions of NR2B and BDNF, which were increased after PTZ kindling. Low-dose of RIVA showed anticonvulsant properties, while high doses did not. RIVA exerts its anticonvulsant effect probably through NMDAR-BDNF pathways. Our results suggest that the use of RIVA may not be harmful and even reduce seizure severity in epileptic patients with convulsions.
Competing Interests: Declarations. Ethics approval: The study was performed by the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. The experimental protocol was approved by Ondokuz Mayıs University Animal Experiments Local Ethics Committee (Approval No: 2022/35). Competing interest: The authors declare no competing interests.
(© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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