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PTZ-induced seizures in rats: effects of age and strain
I A Klioueva1, E L van Luijtelaar, N E Chepurnova
1Department of Human and Animal Physiology, Moscow State University, Moscow, Russia.
Insights
Pentylenetetrazol (PTZ)-induced seizure susceptibility in rats changes with age, peaking around postnatal day 26. Genetically epilepsy-prone WAG/Rij rats show greater vulnerability to PTZ-induced seizures than Wistar rats.
Area of Science:
- Neuroscience
- Epilepsy Research
- Developmental Neurobiology
Background:
- Understanding seizure susceptibility during development is crucial for epilepsy research.
- Pentylenetetrazol (PTZ) is a widely used chemoconvulsant to model seizure activity.
- The WAG/Rij rat strain is genetically predisposed to absence epilepsy, offering a model for studying epilepsy development.
Purpose of the Study:
- To investigate the age-dependent changes in PTZ-induced seizure susceptibility in two rat strains.
- To compare seizure thresholds between WAG/Rij rats and Wistar rats during postnatal development.
- To determine if genetic predisposition to epilepsy influences susceptibility to PTZ-induced convulsive seizures.
Main Methods:
- Two rat strains, WAG/Rij and Wistar, were tested at various postnatal days (PN 10-220).
- PTZ (25 mg/kg) was administered every 15 minutes, and seizure occurrence (clonic and tonic-clonic) was recorded.
- The PTZ-convulsive threshold and latency were measured to assess seizure susceptibility.
Main Results:
- Young pups (PN 10) exhibited high sensitivity to PTZ, primarily showing clonic seizures.
- The highest seizure threshold and longest latency were observed around PN 26 in both strains.
- Seizure susceptibility increased with age from PN 26, reaching a minimum threshold by PN 220.
- WAG/Rij rats demonstrated a significantly lower tonic-clonic seizure threshold compared to Wistar rats.
Conclusions:
- PTZ-induced seizure susceptibility in rats undergoes significant developmental changes, decreasing rapidly until PN 26-30 and then increasing with age.
- Genetically epilepsy-prone WAG/Rij rats are more susceptible to PTZ-induced convulsive seizures than Wistar rats, despite their predisposition to non-convulsive epilepsy.
- These findings highlight the complex interplay between genetic factors, developmental stage, and seizure susceptibility.
Abstract:
The susceptibility to pentylenetetrazol (PTZ)-induced seizures during postnatal ontogeny [postnatal day (PN) 10-220] was investigated in two rat strains. The WAG/Rij strain, genetically prone for developing generalized absence epilepsy, and Wistar rats were tested and compared at PN 10, 26, 30, 70, 90, 125, and 220 on the PTZ-convulsive threshold. A subconvulsive dose of 25-mg/kg PTZ was administered every 15 min, and the occurrence of clonic and tonic-clonic seizures was scored. The 10-day-old pups were quite sensitive to PTZ and showed mainly clonic seizures. The highest threshold and latency of PTZ-induced clonic and tonic-clonic convulsions were observed at PN 26 in both strains. From that age onwards, the seizure threshold significantly decreased and reached a minimum at PN 220. Between strain comparisons showed that WAG/Rij rats have a lower tonic-clonic seizure threshold than Wistar rats. The data indicate that changes in susceptibility first quickly decreases until PN 26-30 and then tend to monotonically increase with age, and that genetically prone nonconvulsive WAG/Rij rats are more vulnerable to convulsive seizures induced by PTZ than Wistar rats.