Rationale: Pentylenetetrazole (PTZ) is a GABA-A receptor antagonist commonly used to induce both acute and chronic seizures in rodent models of epilepsy. The acute PTZ-induced epilepsy model is a straightforward approach to evoke stereotypic seizures. Acute PTZ models are inconsistent across studies, with different injection types and endpoints, making it difficult to compare or replicate results and evaluate potential treatments. To address these knowledge gaps, we systematically evaluated the literature to identify critical variables known to influence animal models of epilepsy. Methods: We performed a comprehensive literature review of studies from the past ten years (2010-2020) using a PubMed search with the following keywords: pentylenetetrazole OR PTZ AND mouse AND seizure OR epilepsy NOT kindling. Our search yielded 130 results, and 99 were included in our analysis. Papers were excluded post hoc if they were review articles, kindling models otherwise not omitted, PTZ paradigms in zebrafish or rat models, and/or evaluations of PTZ as a treatment, not seizure paradigm. We recorded background strain, age, and sex of experimental mice and route of PTZ administration, dose, and primary endpoints from each study. We systematically evaluated if these critical variables were included in the cohort. A variable was considered omitted if there was no mention of it or there was insufficient detail to replicate the study. Results: We found that the majority (53.5%, 53/99) of studies administer PTZ intraperitoneally (IP). Of the studies that used IP PTZ, only 35.8% (19/53) specified the age, sex, and background strain. The majority of IP papers (64.2%, 34/53) omitted one or more of these fields, with 45.3% (24/53) missing one field and 18.9% (10/53) missing two or more fields. The most common field omitted by IP papers was age (50.9%, 27/53), then sex (26.4%, 14/53), then background (13.2%, 7/53). Conclusions: Our comprehensive literature review demonstrates a critical gap in acute PTZ as a seizure paradigm. We recommend that all studies employing PTZ as a method to induce acute seizures control for and specify in their methods the age, sex, and background strain of experimental animals. Funding: Please list any funding that was received in support of this abstract.: NS107637 NINDS K08 and BCH Career Development Fellowship to CJY.
