Age dependent effects of Retigabine on absence seizure in WAG/Rij rats; an experimental study


Karadenizli S., ŞAHİN D., ATEŞ N.

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, vol.48, no.9, pp.1251-1260, 2021 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 48 Issue: 9
  • Publication Date: 2021
  • Doi Number: 10.1111/1440-1681.13537
  • Journal Name: CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE, SportDiscus, Veterinary Science Database
  • Page Numbers: pp.1251-1260
  • Keywords: absence epilepsy, Retigabine, spike-wave-discharges, POTASSIUM CHANNEL GENE, SPIKE-WAVE DISCHARGES, ANIMAL-MODELS, ANTICONVULSANT RETIGABINE, DIMETHYL-SULFOXIDE, KCNQ2 SUBUNITS, EPILEPSY, ACTIVATION, INHIBITION, EZOGABINE
  • Kocaeli University Affiliated: Yes

Abstract

Retigabine (RTG, Ezogabine, DC23129) is the first neuronal potassium channel opener in the treatment of epilepsy and exerts its effects through the activation of neuronal KCNQ2/3 potassium channels; in higher doses, it acts also on sodium and voltage-gated calcium channels. The aim of this study was to investigate possible age-dependent therapeutic effects of RTG on spike-and-wave discharges (SWD) in an animal model of absence epilepsy using WAG/Rij rats. In this study, 6- and 12-month-old WAG/Rij rats were used. For both age categories, three sub-groups that consisted of one control group (n=7) by the administration of 20% DMSO (control) and two study groups by the administration of 5 mg/kg (n=7) and 15 mg/kg RTG (n=7) were designed. EEG electrodes were placed onto the skull of anaesthetized animals; and baseline EEG was recorded for one hour after a recovery period from surgery. Then, the pre-determined two distinct doses of RTG and 20% DMSO were administered as a solvent via intraperitoneal injections, and EEG was recorded for 3 hours. After injection, both doses of RTG increased the total SWD number and duration of SWD in the first and second hours in 12-month-old rats. These parameters were elevated compared to 6-month-old rats. Age-dependent effects of RTG were observed in SWD activity. Pro-epileptic effects in middle-aged WAG/Rij rats were demonstrated in both RTG doses. Differences in the distribution of KCNQ2/3 channels and switch of GABAergic system from inhibitory to excitatory with age might contribute to increased SWD activity in middle-aged rats.