Effect of two noncompetitive AMPA receptor antagonists GYKI 52466 and GYKI 53405 on vigilance, behavior and spike-wave discharges in a genetic rat model of absence epilepsy

R. Jakus, Marton Graf, Romeo D. Ando, Brigitta Balogh, Istvan Gacsalyi, Gyorgy Levay, Sandor Kantor, G. Bagdy

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

The present study was conducted to investigate the effects of two noncompetitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonists, GYKI 52466 and GYKI 53405 (the racemate of talampanel) on the generation of spike-wave discharges (SWD) parallel with the vigilance and behavioral changes in the genetic absence epilepsy model of WAG/Rij rats. Intraperitoneal (i.p.) administration of GYKI 52466 (1-[4-aminophenyl]-4-methyl- 7,8-methylenedioxy-5H-2,3-benzodiazepine; 3, 10 and 30 mg/kg, i.p.), the prototypic compound of the 2,3-benzodiazepine family, caused a fast dose-dependent increase in the number and cumulative duration of SWD. These changes were accompanied by dose-dependent increase in duration of light slow wave sleep (SWS1) and passive awake, vigilance states associated with the presence of SWD. In addition a short, transient behavioral activation occurred that was followed by strong ataxia and immobility, decrease of active wakefulness and increase in deep slow wave sleep. GYKI 53405 (7-acetyl-5-(4-aminophenyl)-8-methyl-8,9-dihydro-7H-1,3-dioxolo[4,5-b][2,3] benzodiazepine, the racemate of talampanel, 16 mg/kg, i.p.) failed to affect any measure of SWD and vigilance. When used as a pretreatment, GYKI 52466 (10 mg/kg) slightly attenuated SWD-promoting effects of the 5-HT1A receptor agonist 8-OH-DPAT, it decreased cumulative duration and average time of paroxysms. In conclusion, AMPA receptors play moderate role in regulation of epileptic activity, and some of these effects are connected to their effects on vigilance in this model.

Original languageEnglish
Pages (from-to)236-244
Number of pages9
JournalBrain Research
Volume1008
Issue number2
DOIs
Publication statusPublished - May 22 2004

Fingerprint

GYKI 53405
Absence Epilepsy
AMPA Receptors
Genetic Models
GYKI 53655
Benzodiazepines
Sleep
Serotonin 5-HT1 Receptor Agonists
8-Hydroxy-2-(di-n-propylamino)tetralin
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
Receptor, Serotonin, 5-HT1A
Wakefulness
Ataxia
Light
GYKI 52466

Keywords

  • 5-HT receptor
  • Absence epilepsy
  • AMPA receptor
  • Excitatory amino acids: pharmacology
  • Glutamate
  • GYKI 52466
  • GYKI 53405
  • Neurotransmitters, modulators, transporters, and receptors
  • Serotonin
  • Sleep
  • Spike-wave discharge
  • Talampanel

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Effect of two noncompetitive AMPA receptor antagonists GYKI 52466 and GYKI 53405 on vigilance, behavior and spike-wave discharges in a genetic rat model of absence epilepsy. / Jakus, R.; Graf, Marton; Ando, Romeo D.; Balogh, Brigitta; Gacsalyi, Istvan; Levay, Gyorgy; Kantor, Sandor; Bagdy, G.

In: Brain Research, Vol. 1008, No. 2, 22.05.2004, p. 236-244.

Research output: Contribution to journalArticle

Jakus, R. ; Graf, Marton ; Ando, Romeo D. ; Balogh, Brigitta ; Gacsalyi, Istvan ; Levay, Gyorgy ; Kantor, Sandor ; Bagdy, G. / Effect of two noncompetitive AMPA receptor antagonists GYKI 52466 and GYKI 53405 on vigilance, behavior and spike-wave discharges in a genetic rat model of absence epilepsy. In: Brain Research. 2004 ; Vol. 1008, No. 2. pp. 236-244.
@article{5db407683caf4191b68db129fe657400,
title = "Effect of two noncompetitive AMPA receptor antagonists GYKI 52466 and GYKI 53405 on vigilance, behavior and spike-wave discharges in a genetic rat model of absence epilepsy",
abstract = "The present study was conducted to investigate the effects of two noncompetitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonists, GYKI 52466 and GYKI 53405 (the racemate of talampanel) on the generation of spike-wave discharges (SWD) parallel with the vigilance and behavioral changes in the genetic absence epilepsy model of WAG/Rij rats. Intraperitoneal (i.p.) administration of GYKI 52466 (1-[4-aminophenyl]-4-methyl- 7,8-methylenedioxy-5H-2,3-benzodiazepine; 3, 10 and 30 mg/kg, i.p.), the prototypic compound of the 2,3-benzodiazepine family, caused a fast dose-dependent increase in the number and cumulative duration of SWD. These changes were accompanied by dose-dependent increase in duration of light slow wave sleep (SWS1) and passive awake, vigilance states associated with the presence of SWD. In addition a short, transient behavioral activation occurred that was followed by strong ataxia and immobility, decrease of active wakefulness and increase in deep slow wave sleep. GYKI 53405 (7-acetyl-5-(4-aminophenyl)-8-methyl-8,9-dihydro-7H-1,3-dioxolo[4,5-b][2,3] benzodiazepine, the racemate of talampanel, 16 mg/kg, i.p.) failed to affect any measure of SWD and vigilance. When used as a pretreatment, GYKI 52466 (10 mg/kg) slightly attenuated SWD-promoting effects of the 5-HT1A receptor agonist 8-OH-DPAT, it decreased cumulative duration and average time of paroxysms. In conclusion, AMPA receptors play moderate role in regulation of epileptic activity, and some of these effects are connected to their effects on vigilance in this model.",
keywords = "5-HT receptor, Absence epilepsy, AMPA receptor, Excitatory amino acids: pharmacology, Glutamate, GYKI 52466, GYKI 53405, Neurotransmitters, modulators, transporters, and receptors, Serotonin, Sleep, Spike-wave discharge, Talampanel",
author = "R. Jakus and Marton Graf and Ando, {Romeo D.} and Brigitta Balogh and Istvan Gacsalyi and Gyorgy Levay and Sandor Kantor and G. Bagdy",
year = "2004",
month = "5",
day = "22",
doi = "10.1016/j.brainres.2004.01.087",
language = "English",
volume = "1008",
pages = "236--244",
journal = "Brain Research",
issn = "0006-8993",
publisher = "Elsevier",
number = "2",

}

TY - JOUR

T1 - Effect of two noncompetitive AMPA receptor antagonists GYKI 52466 and GYKI 53405 on vigilance, behavior and spike-wave discharges in a genetic rat model of absence epilepsy

AU - Jakus, R.

AU - Graf, Marton

AU - Ando, Romeo D.

AU - Balogh, Brigitta

AU - Gacsalyi, Istvan

AU - Levay, Gyorgy

AU - Kantor, Sandor

AU - Bagdy, G.

PY - 2004/5/22

Y1 - 2004/5/22

N2 - The present study was conducted to investigate the effects of two noncompetitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonists, GYKI 52466 and GYKI 53405 (the racemate of talampanel) on the generation of spike-wave discharges (SWD) parallel with the vigilance and behavioral changes in the genetic absence epilepsy model of WAG/Rij rats. Intraperitoneal (i.p.) administration of GYKI 52466 (1-[4-aminophenyl]-4-methyl- 7,8-methylenedioxy-5H-2,3-benzodiazepine; 3, 10 and 30 mg/kg, i.p.), the prototypic compound of the 2,3-benzodiazepine family, caused a fast dose-dependent increase in the number and cumulative duration of SWD. These changes were accompanied by dose-dependent increase in duration of light slow wave sleep (SWS1) and passive awake, vigilance states associated with the presence of SWD. In addition a short, transient behavioral activation occurred that was followed by strong ataxia and immobility, decrease of active wakefulness and increase in deep slow wave sleep. GYKI 53405 (7-acetyl-5-(4-aminophenyl)-8-methyl-8,9-dihydro-7H-1,3-dioxolo[4,5-b][2,3] benzodiazepine, the racemate of talampanel, 16 mg/kg, i.p.) failed to affect any measure of SWD and vigilance. When used as a pretreatment, GYKI 52466 (10 mg/kg) slightly attenuated SWD-promoting effects of the 5-HT1A receptor agonist 8-OH-DPAT, it decreased cumulative duration and average time of paroxysms. In conclusion, AMPA receptors play moderate role in regulation of epileptic activity, and some of these effects are connected to their effects on vigilance in this model.

AB - The present study was conducted to investigate the effects of two noncompetitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonists, GYKI 52466 and GYKI 53405 (the racemate of talampanel) on the generation of spike-wave discharges (SWD) parallel with the vigilance and behavioral changes in the genetic absence epilepsy model of WAG/Rij rats. Intraperitoneal (i.p.) administration of GYKI 52466 (1-[4-aminophenyl]-4-methyl- 7,8-methylenedioxy-5H-2,3-benzodiazepine; 3, 10 and 30 mg/kg, i.p.), the prototypic compound of the 2,3-benzodiazepine family, caused a fast dose-dependent increase in the number and cumulative duration of SWD. These changes were accompanied by dose-dependent increase in duration of light slow wave sleep (SWS1) and passive awake, vigilance states associated with the presence of SWD. In addition a short, transient behavioral activation occurred that was followed by strong ataxia and immobility, decrease of active wakefulness and increase in deep slow wave sleep. GYKI 53405 (7-acetyl-5-(4-aminophenyl)-8-methyl-8,9-dihydro-7H-1,3-dioxolo[4,5-b][2,3] benzodiazepine, the racemate of talampanel, 16 mg/kg, i.p.) failed to affect any measure of SWD and vigilance. When used as a pretreatment, GYKI 52466 (10 mg/kg) slightly attenuated SWD-promoting effects of the 5-HT1A receptor agonist 8-OH-DPAT, it decreased cumulative duration and average time of paroxysms. In conclusion, AMPA receptors play moderate role in regulation of epileptic activity, and some of these effects are connected to their effects on vigilance in this model.

KW - 5-HT receptor

KW - Absence epilepsy

KW - AMPA receptor

KW - Excitatory amino acids: pharmacology

KW - Glutamate

KW - GYKI 52466

KW - GYKI 53405

KW - Neurotransmitters, modulators, transporters, and receptors

KW - Serotonin

KW - Sleep

KW - Spike-wave discharge

KW - Talampanel

UR - http://www.scopus.com/inward/record.url?scp=2442492165&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=2442492165&partnerID=8YFLogxK

U2 - 10.1016/j.brainres.2004.01.087

DO - 10.1016/j.brainres.2004.01.087

M3 - Article

C2 - 15145761

AN - SCOPUS:2442492165

VL - 1008

SP - 236

EP - 244

JO - Brain Research

JF - Brain Research

SN - 0006-8993

IS - 2

ER -