Factors influencing the acute pentylenetetrazole‐induced seizure paradigm and a literature review

OBJECTIVE: To confirm the critical factors affecting seizure susceptibility in acute pentylenetetrazole (PTZ) mouse epilepsy models and evaluate the prior literature for these factors. METHODS: Serial cohorts of wild‐type mice administered intraperitoneal (IP)‐PTZ were aggregated and analyzed by multivariate logistic regression for the effect of sex, age, background strain, dose, and physiologic stress (i.e., EEG implantation and/or single‐housing) on seizure response. We assessed the reporting of these factors in a comprehensive literature review over the last 10 years (2010–2020). RESULTS: We conducted aggregated analysis of pooled data of 307 mice (220 C57BL/6J mice and 87 mixed background mice; 202 males, 105 females) with median age of 10 weeks (range: 6–49 weeks) with acute PTZ injection (dose range 40–65 mg/kg). Significance in multivariate analysis was found between seizures and increased PTZ dose (odds ratio (OR) 1.149, 95% confidence interval (CI) 1.102–1.205), older age (OR 1.1, 95% CI 1.041–1.170), physiologic stress (OR 17.36, 95% CI 7.349–44.48), and mixed background strain (OR 0.4725, 95% CI 0.2315–0.9345). Literature review identified 97 papers using acute PTZ‐seizure models. Age, housing, sex, and background were omitted by 61% (59/97), 51% (49/97), 18% (17/97), and 8% (8/97) papers, respectively. Only 17% of publications specified all four factors (16/97). INTERPRETATION: Our analysis and literature review demonstrate a critical gap in standardization of acute PTZ‐induced seizure paradigm in mice. We recommend that future studies specify and control for age, background strain, sex, and housing conditions of experimental animals.