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Pharmacol Biochem Behav. 2019 May 10. pii: S0091-3057(19)30022-X. doi: 10.1016/j.pbb.2019.04.010. [Epub ahead of print]

The effect of co-administration of pentylenetetrazole with pilocarpine: New modified PTZ models of kindling and seizure.

Author information

1
Department of Physiology, Faculty of Medicine, Arak University of Medical Sciences, Arak, IR, Iran.
2
Students Research Committee, Faculty of Medicine, Arak University of Medical Sciences, Arak, IR, Iran; Department of Neurology and Interventional Neuroradiology, Isfahan University of Medical Sciences, Isfahan, Iran.
3
Department of Physiology, Faculty of Medicine, Arak University of Medical Sciences, Arak, IR, Iran. Electronic address: dr.palizvan@arakmu.ac.ir.

Abstract

BACKGROUND:

Drug resistance is a major problem in the treatment of epilepsy. There is a critical need for new epilepsy models to evaluate antiepileptic compounds. Pentylenetetrazole- (PTZ) and pilocarpine-induced seizures are well-established models of human epilepsy. Generally, PTZ or pilocarpine has been used to produce seizures in experimental models. In this study, we explored the possibility of creating new epilepsy and seizure models by co-administration of PTZ and pilocarpine.

METHODS:

The protocol was divided into three parts: A) Kindling experiments: the animals received PTZ or co-administration doses of PTZ and pilocarpine every other day for a period of 26 days. B) Seizure experiments, for induction of seizure, the animals received one dose of PTZ, pilocarpine or co-administration doses of PTZ and pilocarpine. C) Evaluation of antiepileptic drugs: the animals received phenytoin or sodium valproate 20 min before injection of PTZ, pilocarpine or co-administration doses of PTZ and pilocarpine.

RESULTS:

The co-administration of pilocarpine and PTZ could induce seizure, which has behavioral similarity between electrical and chemical kindling. Pilocarpine (50 mg/kg) + PTZ (37.5 mg/kg) was the appropriate dose for kindling induction. Animals with this dose reached the stage five seizures significantly faster than those with PTZ alone. Unlike the seizure induced by PTZ, or pilocarpine, induction of seizure by PTZ + pilocarpine was resistant to phenytoin and sodium valproate treatment. As compared to the PTZ model of kindling, this model visualized the seizure behavior better and had resistance to two most popular antiepileptic drugs.

CONCLUSION:

Our results indicated that co-administration of pilocarpine and PTZ could provide a new modified model of seizure and kindling resisting to phenytoin and sodium valproate.

KEYWORDS:

Kindling; Pentylenetetrazole; Phenytoin; Pilocarpine; Seizure; Sodium valproate

PMID:
31082418
DOI:
10.1016/j.pbb.2019.04.010

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