Modified Pentylenetetrazole Model for Acute Seizure Induction in Rats

Background/Objectives: Acute seizure models are widely used in epilepsy research to investigate seizure mechanisms and evaluate antiseizure drug efficacy. Among these models, pentylenetetrazole (PTZ)-induced seizures provide a controlled and reproducible approach to study acute seizure dynamics. However, existing PTZ protocols often suffer from inconsistent seizure induction, high mortality rates, and limited translational relevance. Methods: In this study, we systematically evaluated different PTZ dosing regimens in adult Sprague-Dawley rats to establish an optimized acute seizure model that balances seizure induction efficiency with minimal lethality. Results: We tested multiple PTZ administration protocols, identifying a two-step regimen of 50 mg/kg followed by 30 mg/kg (30 min later) as the most effective strategy. This dosing approach reliably induced generalized tonic-clonic seizures in 94% of the animals while eliminating mortality. Seizures induced by this regimen were validated through electrocorticography (ECoG) recordings. The behavioral and ECoG assessments of seizures showed a strong agreement in the latency and duration (r = 0.97, p < 0.0001; r = 0.81, p < 0.05, respectively) with minimal bias in Bland–Altman analysis, confirming that both methods provide statistically comparable and interchangeable measures of seizure characteristics. Conclusions: Our findings highlight the robustness and reproducibility of this modified PTZ-induced acute seizure model, offering an improved preclinical platform for studying seizure pathophysiology and screening for novel therapeutic interventions.