In:
Epilepsia, Wiley, Vol. 56, No. 11 ( 2015-11), p. 1793-1802
Abstract:
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 SNR anterior and SNR posterior 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 ; GABA ergic 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 SNR anterior or SNR posterior . In another experiment, PRV ‐ir in SNR anterior and SNR posterior and TH ‐ir in SNR posterior only were densitometrically compared in GAERS ‐ SHAM , NEC ‐ SHAM GAERS ‐ STIM , and NEC ‐ STIM animals (6 kindling stimulations). Results Bilateral SNR posterior infusions of lidocaine eliminated the kindling resistance and resulted in stage 5 generalized motor seizures in all kindled rats. Bilateral lidocaine infusions in the SNR anterior failed to alter the kindling resistance in GAERS . PRV ‐ir in the SNR posterior was unaltered in GAERS ‐ STIM but increased in NEC ‐ STIM group. Cellular TH ‐ir in the SNR posterior significantly increased by kindling stimulations in both NEC ‐ STIM and GAERS ‐ STIM groups. Significance The kindling resistance in GAERS is mediated by the SNR posterior in a lidocaine‐sensitive manner. The insensitivity to kindling stimulation of PRV ‐ir in SNR posterior of GAERS but not NEC rats, implicate GABA ergic SNR posterior neurons in kindling resistance. In contrast, the observed stimulation‐specific increase in TH ‐ir in the SNR posterior is unrelated to kindling resistance.
Type of Medium:
Online Resource
ISSN:
0013-9580
,
1528-1167
DOI:
10.1111/epi.2015.56.issue-11
Language:
English
Publisher:
Wiley
Publication Date:
2015
detail.hit.zdb_id:
2002194-X
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