title: The role of the substantia nigra pars reticulata in kindling resistance in rats with genetic absence epilepsy.
abstract: OBJECTIVE
  Genetic Absence Epilepsy Rats from Strasbourg (GAERS) show a resistance to secondary generalization of focal limbic seizures evoked by kindling. The substantia nigra pars reticulata (SNR) is involved in the propagation and modulation of seizures in kindling. We first examined the role of the SNRanterior and SNRposterior subregions in the resistance to the development of kindling in GAERS. Subsequently, to determine whether kindling resistance relates to differential sensitivity of γ-aminobutyric acid γ-aminobutyric acid (GABA)ergic or dopaminergic SNR neurons to kindling, we studied the effects of kindling-inducing stimulations on parvalbumin (PRV; GABAergic neuron marker) or tyrosine hydroxylase (TH; dopaminergic neuron marker) immunoreactivity (ir), respectively, in GAERS and in nonepileptic control (NEC) Wistar rats that lack kindling resistance.
  
  
  METHODS
  Adult male GAERS were implanted with a stimulation electrode in the amygdala, and bilateral injection cannulas for lidocaine or saline injection (30 min before each kindling stimulation until the animals reached three stage 5 seizures or the 22 stimulations) into the SNRanterior or SNRposterior . In another experiment, PRV-ir in SNRanterior and SNRposterior and TH-ir in SNRposterior only were densitometrically compared in GAERS-SHAM, NEC-SHAM GAERS-STIM, and NEC-STIM animals (6 kindling stimulations).
  
  
  RESULTS
  Bilateral SNRposterior infusions of lidocaine eliminated the kindling resistance and resulted in stage 5 generalized motor seizures in all kindled rats. Bilateral lidocaine infusions in the SNRanterior failed to alter the kindling resistance in GAERS. PRV-ir in the SNRposterior was unaltered in GAERS-STIM but increased in NEC-STIM group. Cellular TH-ir in the SNRposterior significantly increased by kindling stimulations in both NEC-STIM and GAERS-STIM groups.
  
  
  CONCLUSIONS
  The kindling resistance in GAERS is mediated by the SNRposterior in a lidocaine-sensitive manner. The insensitivity to kindling stimulation of PRV-ir in SNRposterior of GAERS but not NEC rats, implicate GABAergic SNRposterior neurons in kindling resistance. In contrast, the observed stimulation-specific increase in TH-ir in the SNRposterior is unrelated to kindling resistance.
authors.affiliation: Department of Physiology, Faculty of Medicine, Istanbul Bilim University, Istanbul, Turkey.
authors.forename: Ozlem
authors.initials: O
authors.lastname: Akman
authors.affiliation: Department of Pharmacology and Clinical Pharmacology, Faculty of Medicine, Marmara University, Istanbul, Turkey.
authors.forename: Medine I
authors.initials: MI
authors.lastname: Gulcebi
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Istanbul University, Istanbul, Turkey.
authors.forename: Nihan
authors.initials: N
authors.lastname: Carcak
authors.affiliation: Department of Pharmacology and Clinical Pharmacology, Faculty of Medicine, Marmara University, Istanbul, Turkey.|Vocational School of Health Service, Istanbul Bilim University, Istanbul, Turkey.
authors.forename: Sema
authors.initials: S
authors.lastname: Ketenci Ozatman
authors.affiliation: Department of Pharmacology and Clinical Pharmacology, Faculty of Medicine, Marmara University, Istanbul, Turkey.
authors.forename: Tugba
authors.initials: T
authors.lastname: Eryigit
authors.affiliation: Laboratory of Developmental Epilepsy, Saul R. Korey Department of Neurology, Montefiore Epilepsy Management Center, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York, U.S.A.|Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York, U.S.A.|Department of Pediatrics, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York, U.S.A.
authors.forename: Solomon L
authors.initials: SL
authors.lastname: Moshé
authors.affiliation: Laboratory of Developmental Epilepsy, Saul R. Korey Department of Neurology, Montefiore Epilepsy Management Center, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York, U.S.A.|Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York, U.S.A.
authors.forename: Aristea S
authors.initials: AS
authors.lastname: Galanopoulou
authors.affiliation: Department of Pharmacology and Clinical Pharmacology, Faculty of Medicine, Marmara University, Istanbul, Turkey.|Epilepsy Research Center, Marmara University, Istanbul, Turkey.
authors.forename: Filiz Yilmaz
authors.initials: FY
authors.lastname: Onat
mesh_terms: D000818:Animals; D004558:Electric Stimulation / Q000009:adverse effects; D004832:Epilepsy, Absence / Q000209:etiology / Q000235:genetics* / Q000473:pathology*; D007696:Kindling, Neurologic / Q000502:physiology*; D008297:Male; D065841:Pars Reticulata / Q000473:pathology* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar
keywords: GAERS; Kindling resistance; Parvalbumin; Substantia nigra pars reticulata; Tyrosine hydroxylase