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The use of zebrafish as a model organism is gaining evidence in the field of epilepsy as it may help to understand the mechanisms underlying epileptic seizures. As zebrafish assays became popular, the heterogeneity between protocols increased, making it hard to choose a standard protocol to conduct research while also impairing the comparison of results between studies. We conducted a systematic review to comprehensively profile the chemically-induced seizure models in zebrafish. Literature searches were performed in PubMed, Scopus, and Web of Science, followed by a two-step screening process based on inclusion/exclusion criteria. Qualitative data were extracted, and a sample of 100 studies was randomly selected for risk of bias assessment. Out of the 1058 studies identified after removing duplicates, 201 met the inclusion criteria. We found that the most common chemoconvulsants used in the reviewed studies were pentylenetetrazole (n = 180), kainic acid (n = 11), and pilocarpine (n = 10), which increase seizure severity in a dose-dependent manner. The main outcomes assessed were seizure scores and locomotion. Significant variability between the protocols was observed for administration route, duration of exposure, and dose/concentration. Of the studies subjected to risk of bias assessment, most were rated as low risk of bias for selective reporting (94%), baseline characteristics of the animals (67%), and blinded outcome assessment (54%). Randomization procedures and incomplete data were rated unclear in 81% and 68% of the studies, respectively. None of the studies reported the sample size calculation. Overall, these findings underscore the need for improved methodological and reporting practices to enhance the reproducibility and reliability of zebrafish models for studying epilepsy. Our study offers a comprehensive overview of the current state of chemically-induced seizure models in zebrafish, highlighting the common chemoconvulsants used and the variability in protocol parameters. This may be particularly valuable to researchers interested in understanding the underlying mechanisms of epileptic seizures and screening potential drug candidates in zebrafish models., Competing Interests: Conflict of interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background & Aims: Animal models provide crucial tools to study epilepsy which is one of the most common neurological disorder. Experimental models are valid and essential to discover new antiepileptic drugs as well as to elucidate circuitry dysfunction of disease. Therefore, in this review, we summarize the prominent used methods for induction experimental seizures and epilepsy induced by electrical, chemoconvulsants, traumatic brain injury, acoustic stimulation as well as hyperthermia and hypoxia condition. Material and Methods: In this review data were collected through searching electronic databases of PubMed and Google Scholar for several methods of induction seizure and epilepsy in experimental animals. Results: The maximal electroshock (MES), pentylentetrazole (PTZ), and 6-Hz seizure models are three simple seizure models for inducing acute seizure in intact animal. The pilocarpine, kainic acid, antibiotics, metals and organophosphorus compounds have epileptogenic potency for inducing motor seizures. The most common type of chronic models of epilepsy are electrical kindling, PTZ-induced kindling and transgenic models. Pharmacoresistance models include the phenytoin- or lamotrigine-pretreated kindled rats model, the 6-Hz mouse model, pentylentetrazole induced seizures in rats pre-exposed to pilocarpine and intrauterine exposure of rats to methylazoxymethanol. Lastly, Posttraumatic epilepsy, audiogenic seizures, hyperthermia and neonatal hypoxia model as well as in vitro models are used to induce and study seizures. Conclusion: Epilepsy and seizure in experimental animals can be modeled by several factors include acute and chronic stimulation, mechanical insults and changing environmental conditions in both forms in vivo and vitro.

Abstract: Larval zebrafish (Danio rerio) have recently been suggested as a high-throughput experimental model of epilepsy-related pathogenetic states. Here we use adult zebrafish to study behavioral symptoms associated with drug-evoked seizures. Experimental epilepsy-like states were evoked in zebrafish by exposure for 20min to three chemoconvulsant drugs: caffeine (250mg/L; 1.3mM), pentylenetetrazole (1.5g/L; 11.0mM) and picrotoxin (100mg/L; 0.17mM). Fish behavior was analyzed using manual and video-tracking methods (Noldus Ethovision XT7). Compared to their respective controls, all three drug-treated groups showed robust seizure-like responses (hyperactivity bouts, spasms, circular and corkscrew swimming) accompanied by elevated whole-body cortisol levels (assessed by ELISA). In contrast, control fish did not display seizure-like behaviors and had significantly lower cortisol levels. Paralleling behavioral and endocrine phenotypes observed in clinical and rodent studies, our data implicates adult zebrafish as an emerging experimental model for epilepsy research. [ABSTRACT FROM AUTHOR]