Pentylenetetrazol-induced kindling in rats: Effect of GABA function inhibitors

Corda, Maria Giuseppa; Orlandi, M; Lecca, Daniele; Carboni, Giulia; Frau, V; Giorgi, Osvaldo

doi:10.1016/0091-3057(91)90562-g

Cited by 95 publications

(41 citation statements)

References 25 publications

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“…[25] Repetitive single dose application ends up with decreased GABAergic activity. [35] PTZ is claimed to exert its activity via inhibiting gammaaminobutyric acid (GABA) activated channels.…”

Section: Alterations In Gabaergic Systemsmentioning

confidence: 99%

Pentylenetetrazol Kindling Epilepsy Model

Erkeç¹,

Arıhan²

2015

Epilepsi

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SummaryEpilepsy is one of the most common neurologic disorders affecting approximately 1% of the general population, and no alleviation was achieved in one third of the patients medicated with antiepileptic drugs. Current treatments of epilepsy are symptomatic and have more anti-seizure effects than antiepileptic effects. These therapies do not cure epilepsy. Basic mechanisms of epilepsy have not entirely been clarified yet. Using seizure and epilepsy animal models, our comprehension about basic mechanisms underlying epileptogenesis has improved. In addition, animal models of epilepsy and seizures are very useful in the discovery and development of new antiepileptic drugs. Pentylenetetrazole (PTZ) is widely used in antiepileptic drug discovery studies, and PTZ kindling model is very important to understand the pathophysiology of epilepsy. In this review, current information about PTZ kindling model was given in this aspect.Key words: Chemical kindling; epilepsy; experimental animal models; pentylenetetrazole; rat. ÖzetEpilepsi genel popülasyonun yaklaşık %1'ini etkileyen en yaygın nörolojik düzensizliklerden biridir. Antiepileptik ilaç tedavisi gören hastaların üçte birinde hiçbir hafifleme elde edilememektedir. Epilepsi için kullanılan güncel tedaviler semptomatiktir ve antiepileptik etkiden ziyade anti nöbet etkilidir. Bu tedaviler epilepsiyi tedavi etmemektedir. Epilepsinin temel mekanizmaları da henüz tam olarak anlaşılamamıştır. Nö-bet ve epilepsi hayvan modelleri kullanılarak epilepsinin temelinde yatan mekanizmaları kavrayışımız ilerlemektedir. Ayrıca epilepsi ve nöbet hayvan modelleri yeni antiepileptik ilaç keşfi ve gelişimi bakımından kullanışlıdırlar. Pentilentetrazol (PTZ), antiepileptik ilaç keşif çalışmala-rında yaygın biçimde kullanılmaktadır ve PTZ tutuşma modeli epilepsinin patofizyolojisinin anlaşılması bakımından oldukça önemlidir. Bu

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Section: Alterations In Gabaergic Systemsmentioning

confidence: 99%

Pentylenetetrazol Kindling Epilepsy Model

Erkeç¹,

Arıhan²

2015

Epilepsi

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“…For comparison, we treated mice with a minimally convulsant dose of PTZ (Sigma-Aldrich; 35 mg/kg i.p. in sterile water) on a 48-h dose schedule, which led to permanent augmentation of the seizure response (kindling) (Corda et al, 1991). Immediately after dosing, the animals were observed for 60 min in the case of TETS or 30 min in the case of PTZ for the occurrence of seizure signs, which were rated on the basis of a modified Racine scoring system (Racine, 1972), in which points were assessed as follows: 0, no response; 1, immobility; 2, brief myoclonic body jerks; and 3, clonic seizures (repetitive clonic jerking of forelimbs or forelimbs and hindlimbs bilaterally that persist for at least 5 s).…”

Section: Zolkowska Et Almentioning

confidence: 99%

“…Moreover, there was no persistent enhanced seizure susceptibility when animals treated with repeated doses of TETS were exposed to a subthreshold challenge dose of PTZ 7 days after the last dose of TETS. It has been demonstrated previously that chemical kindling with one GABA A receptor antagonist results in a persistent reduced threshold for other GABA A receptor antagonists such as PTZ (Grecksch et al, 1990;Corda et al, 1991;De Sarro et al, 1999). The failure of TETS to cause chemical kindling represents a difference from other GABA A receptor antagonists.…”

mentioning

confidence: 98%

Characterization of Seizures Induced by Acute and Repeated Exposure to Tetramethylenedisulfotetramine

Żółkowska

Banks

Dhir

et al. 2012

J Pharmacol Exp Ther

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Tetramethylenedisulfotetramine (tetramine; TETS) is a potent convulsant poison that is considered to be a chemical threat agent. To provide a basis for the investigation of antidotes for TETS-induced seizures, we characterized the convulsant activity of TETS in mice and rats when administered by the intraperitoneal, intravenous, oral, and intraventricular routes as a single acute dose and with repeated sublethal doses. In mice, parenteral and oral TETS caused immobility, myoclonic body jerks, clonic seizures of the forelimbs and/or hindlimbs, tonic seizures, and death. The CD 50 values for clonic and tonic seizures after oral administration were 0.11 and 0.22 mg/kg, respectively. Intraventricular administration of TETS (5-100 g) in rats also caused clonic-tonic seizures and death. In mice, repeated sublethal doses of TETS at intervals of 2, 24, and 48 h failed to result in the development of persistent enhanced seizure responsivity ("kindling") as was observed with repeated pentylenetetrazol treatment. In mice, sublethal doses of TETS that produced clonic seizures did not cause observable structural brain damage as assessed with routine histology and Fluoro-Jade B staining 7 days after treatment. However, 1 to 3 days after a single convulsant dose of TETS the expression of glial fibrillary acidic protein, an astrocyte marker, and ionized calcium binding adaptor molecule 1, a microglia marker, were markedly increased in cortex and hippocampus. Although TETS doses that are compatible with survival are not associated with overt evidence of cellular injury or neurodegeneration, there is transient reactive astrocytosis and microglial activation, indicating that brain inflammatory responses are provoked.

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“…Mice were placed in acrylic observation chambers and the behavior of each mouse was observed for 1 h after the injection. Seizure intensity was scored according to Corda et al (1991): a score of 0 was given for no response; 1 for ear and facial twitching; 2 for myoclonic body jerks; 3 for clonic forelimb convulsions; 4 for generalized convulsions with tonic extension episode and status epilepticus; and 5 for death. Experiments started with 21 animals of each genotype and the mice exhibiting a seizure phenotype scoring Ն were removed from the pool.…”

Section: Pentylenetetrazole (Ptz)-induced Seizuresmentioning

confidence: 99%

Hyperexcitability and epilepsy associated with disruption of the mouse neuronal‐specific K–Cl cotransporter gene

et al. 2002

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Four genes encode electroneutral, Na+-independent, K-Cl cotransporters. KCC2, is exclusively expressed in neurons where it is thought to drive intracellular Cl- to low concentrations and shift the reversal potential for Cl- conductances such as GABA(A) or glycine receptor channels, thus participating in the postnatal development of inhibitory mechanisms in the brain. Indeed, expression of the cotransporter is low at birth and increases postnatally, at a time when the intracellular Cl- concentration in neurons decreases and gamma-aminobutyric acid switches its effect from excitatory to inhibitory. To assert the significance of KCC2 in neuronal function, we disrupted the mouse gene encoding this neuronal-specific K-Cl cotransporter. We demonstrate that animals deficient in KCC2 exhibit frequent generalized seizures and die shortly after birth. We also show upregulation of Fos, the product of the immediate early gene c-fos, and the significant loss of parvalbumin-positive interneurons, both indicative of brain injury. The regions most affected are the hippocampus and temporal and entorhinal cortices. Extracellular field potential measurements in the CA1 hippocampus exhibited hyperexcitability. Application of picrotoxin, a blocker of the GABA(A) receptor, further increased hyperexcitability in homozygous hippocampal sections. Pharmacological treatment of pups showed that diazepam relieved the seizures while phenytoin prevented them between postnatal ages P4-P12. Finally, we demonstrate that adult heterozygote animals show increased susceptibility for epileptic seizure and increased resistance to the anticonvulsant effect of propofol. Taken together, these results indicate that KCC2 plays an important role in controlling CNS excitability during both postnatal development and adult life.

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Pentylenetetrazol-induced kindling in rats: Effect of GABA function inhibitors

Cited by 95 publications

References 25 publications

Pentylenetetrazol Kindling Epilepsy Model

Pentylenetetrazol Kindling Epilepsy Model

Characterization of Seizures Induced by Acute and Repeated Exposure to Tetramethylenedisulfotetramine

Hyperexcitability and epilepsy associated with disruption of the mouse neuronal‐specific K–Cl cotransporter gene

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