Substantia nigra pars reticulata lesion facilitates kainic acid-induced seizures

doi:10.1016/S0006-8993(00)02620-2

Brain Research

Volume 877, Issue 1, 15 September 2000, Pages 107-109

https://doi.org/10.1016/S0006-8993(00)02620-2 Get rights and content

Abstract

The administration of subconvulsive doses of kainic acid (5 mg/kg, intraperitoneally) to rats, with lesion of the substantia nigra pars reticulata (1 week), produced high frequency wet dog shakes and severe convulsive behavior (observed in 60% of the rats). The behavior was not observed in rats treated with kainic acid but without reticulata lesion. The results show that rats with unilateral lesion of the substantia nigra pars reticulata are more vulnerable to seizure stimuli.

Section snippets

Acknowledgements

Financial support was provided by Saskatchewan Health.

References (12)

Y. Ben-Ari et al.
Injections of kainic acid into the amygdaloid complex of the rat: an electrographic, clinical and histological study in relation to the pathology of epilepsy
Neuroscience
(1980)
X.D. Fan et al.
Substantia nigra pars reticulata lesion induces preconvulsive behavior and changes in glutamate receptor gene expression in the rat brain
Brain Res.
(2000)
X.D. Fan et al.
Induction of preconvulsive behavior and Fos expression by dopamine-induced nigral lesion in the rat
Brain Res.
(1997)
E.W. Lothman et al.
Kainic acid induced limbic seizures: metabolic, behavioral, electroencephalographic and neuropathological correlates
Brain Res.
(1981)
J.W. Olney et al.
Kainic acid: A powerful neurotoxic analogue of glutamate
Brain Res.
(1974)
J.E. Schwob et al.
Widespread patterns of neuronal damage following system or intracerebral injections of kainic acid: a histological study
Neuroscience
(1980)

There are more references available in the full text version of this article.

Cited by (6)

The role of the substantia nigra pars reticulata anterior in amygdala-kindled seizures
2019, Brain Research
Citation Excerpt :
As the main GABAergic output nuclei of the SNr (Velíšková and Moshé, 2006; Gulcebi et al., 2012), the thalamus plays an important role in the propagation of amygdala-kindled seizures to the neocortex (Blumenfeld et al., 2007). Some studies have proposed the hypothesis that a nigro-thalamo-cortical circuit is involved in the control of seizures (Fan et al., 2000a,b). In our experiments, lesion decreased the GABAergic output of the SNra and would result in neuronal disinhibition of the thalamus, which would worsen seizures in fully-kindled mice.
It has been reported that the substantia nigra pars reticulata (SNr) is of regional differences and involved in the initiation, generalization, and cessation of seizures. However, neuropharmacological investigations into the role of the SNr anterior (SNr_a) in temporal lobe epilepsy (TLE) have been inconsistent, suggesting that electrophysiological investigations are needed to elucidate the role of the SNr_a in TLE.
Local field potentials (LFPs) and single-unit activities were simultaneously obtained from the basolateral amygdala (BLA) and the SNr_a in amygdala-kindled mice. The electrophysiological characteristics of the neuronal activities in the BLA and SNr_a were investigated. Directionality index was used to measure information flow between LFPs in the two areas during kindled seizures. The effects of electrical lesion of the SNr_a on the kindled seizures were analyzed in fully-kindled mice.
The information flow was predominantly from the SNr_a to the BLA during the clonic-like periods of stage 5 seizures, but this phenomenon was not found during other kindled seizures. In fully-kindled mice, SNr_a lesions facilitated the kindled seizures. After lesions were inflicted, the afterdischarge durations and clonic-like periods of stage 5 seizures increased significantly.
The electrophysiological and lesion results show that the SNr_a may play an anti-convulsant role in amygdala-kindled seizures.
Intranigral transplants of immortalized GABAergic cells decrease the expression of kainic acid-induced seizures in the rat
2006, Behavioural Brain Research
Repeated systemic administration of low doses of kainic acid (KA) induces spontaneous convulsive seizures [Hellier JL, Patrylo PR, Buckmaster PS, Dudek FE. Recurrent spontaneous motor seizures after repeated low-dose systemic treatment with kainate: assessment of a rat model of temporal lobe epilepsy. Epilepsy Res 1998;31:73–84]. In this study, male Sprague-Dawley animals received intranigral transplants of a control cell line M213-2O, or a cell line transfected with human GAD67 cDNA (M213-2O CL4) [Conejero-Goldberg C, Tornatore C, Abi-Saab W, Monaco MC, Dillon-Carter O, Vawter M, et al. Transduction of human GAD67 cDNA into immortalized striatal cell lines using an Epstein-Barr virus-based plasmid vector increases GABA content. Exp Neurol 2000;161:453–61], or no transplant. Eight weeks after transplantation surgery, KA was administered (5 mg/kg/h) until animals reached stage V seizures as described by Racine [Racine RJ. Modification of seizure activity by electrical stimulation. II. Motor seizure. Electroencephalogr Clin Neurophysiol 1972;32:281–94]. The group transplanted with CL4 required a larger dose of KA and a longer latency to reach a stage V seizure. In addition, this group exhibited significantly fewer stage III and IV seizures. These results indicate that intranigral transplants of a GABA-producing cell line can decrease the number of kainic acid-induced seizures.
Congenital brain dysplasias of different genesis can differently affect susceptibility to pilocarpine- or kainic acid-induced seizures in the rat
2005, Epilepsy Research
Interruption of neurogenesis and/or neuronal migration produces brain dysplasia modifying susceptibility to epileptic seizures in adulthood. The course of neurogenesis has a strictly defined time-table. Consequently, the developmental stage at which the interruption occurs determines what functional subsystem potentially involved in epileptogenesis will suffer from irreversible neuronal deficit. The present study attempts to verify a hypothesis that brain dysplasias of different genesis should also lead to different susceptibility to seizures evoked by receptor agonists of different functional specificity, like kainic acid or pilocarpine, a cholinergic or glutaminergic agonist, respectively. Pregnant Wistar rats were exposed to gamma-rays on gestation days 13, 15, 17 or 19 (E13, E15, E17 or E19). Sixty-day-old offsprings of the females were injected with kainic acid or pilocarpine to evoke status epilepticus. During a 6-h period following the injection, motor manifestations of seizure activity were recorded. Generally, the intensity of pilocarpine-induced symptoms was relatively low in rats irradiated on E13 or E15 but high in rats irradiated on E17 or E19. In rats treated with kainic acid, the trend was opposite, viz. the later the prenatal irradiation was performed, the less intense epileptic symptoms were induced in adulthood. The data provide evidence that dysplasias acquired during prenatal development may significantly amplify or reduce the brain susceptibility to seizures. However, this relation depends not only on the developmental stage at which the dysplasias were produced but also on the functional specificity of epileptogenic stimuli used in the experimental model of epilepsy.
Electrical stimulation of substantia nigra pars reticulata is anticonvulsant in adult and young male rats
2002, Experimental Neurology
Electrical stimulation of deep brain structures has been used for pain relief and treatment of refractory Parkinson's disease. Recently, stimulation of the subthalamic nucleus or anterior nuclei of the thalamus was introduced for the treatment of refractory epilepsy when other treatments failed. The substantia nigra pars reticulata (SNR) is another crucial site involved in the control of seizures. We studied the effects of continuous electrical stimulation of the SNR as a function of age in male rats. Adult [postnatal day (PN) 60] and young (PN 15) rats with electrodes symmetrically implanted in the SNR were used. The rats were stimulated with continuous constant current pulses (130 Hz) and simultaneously challenged with flurothyl to induce seizures. Control rats had the electrodes implanted but were not stimulated. High-frequency electrical stimulation of the SNR had anticonvulsant effects in both age groups. However, we identified age-specific features: In PN 60 rats, both unilateral and bilateral stimulation of the anterior region of the SNR produced anticonvulsant effects against clonic seizures, while stimulation of the posterior region of the SNR was ineffective. Stimulation of either SNR region had no effects on tonic–clonic seizures. In PN 15 rats, irrespective of the stimulation site within the SNR, bilateral stimulations of the SNR produced anticonvulsant effects against both clonic and tonic–clonic flurothyl-induced seizures, while unilateral stimulation was without effect. The data suggest that the SNR may be a candidate site for deep brain stimulation for the treatment of epilepsy.
Not Part of the Temporal Lobe, but Still of Importance? Substantia Nigra and Subthalamic Nucleus in Epilepsy
2020, Frontiers in Systems Neuroscience
The nicotinic acetylcholine receptor subunit α5 mediates short-term effects of nicotine in vivo
2003, Molecular Pharmacology

View full text

Short communicationSubstantia nigra pars reticulata lesion facilitates kainic acid-induced seizures

Abstract

Section snippets

Acknowledgements

Neuroscience

Brain Res.

Brain Res.

Brain Res.

Brain Res.

Neuroscience

Short communication
Substantia nigra pars reticulata lesion facilitates kainic acid-induced seizures