Seizures induced by pentylenetetrazole in the adult zebrafish: a detailed behavioral characterization

• Published in: PloS one 2013-01, Vol.8 (1), p.e54515
• Main Authors: Mussulini, Ben Hur M, Leite, Carlos E, Zenki, Kamila C, Moro, Luana, Baggio, Suelen, Rico, Eduardo P, Rosemberg, Denis B, Dias, Renato D, Souza, Tadeu M, Calcagnotto, Maria E, Campos, Maria M, Battastini, Ana M, de Oliveira, Diogo L
• Format: Article
• Language: English
• Subjects: Adenosine; Analysis; Animal models; Animals; Behavior; Behavior, Animal - drug effects; Behavior, Animal - physiology; Biology; Brain; Brain - drug effects; Brain - physiopathology; Brain research; Convulsants - pharmacology; Convulsions & seizures; Danio rerio; Diazepam; Diazepam - pharmacology; Disease Models, Animal; Dose-Response Relationship, Drug; Epilepsy; Epilepsy - chemically induced; Epilepsy - drug therapy; Epilepsy - physiopathology; Exposure; Gene expression; Genetic aspects; Humans; Medicine; Motor Activity - drug effects; Motor Activity - physiology; Pentylenetetrazole; Pentylenetetrazole - analysis; Pentylenetetrazole - toxicity; Seizing; Seizures; Seizures (Medicine); Swimming; Zebrafish; Zebrafish - abnormalities; Zebrafish - physiology
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0054515

Pentylenetetrazole (PTZ) is a common convulsant agent used in animal models to investigate the mechanisms of seizures. Although adult zebrafish have been recently used to study epileptic seizures, a thorough characterization of the PTZ-induced seizures in this animal model is missing. The goal of this study was to perform a detailed temporal behavior profile characterization of PTZ-induced seizure in adult zebrafish. The behavioral profile during 20 min of PTZ immersion (5, 7.5, 10, and 15 mM) was characterized by stages defined as scores: (0) short swim, (1) increased swimming activity and high frequency of opercular movement, (2) erratic movements, (3) circular movements, (4) clonic seizure-like behavior, (5) fall to the bottom of the tank and tonic seizure-like behavior, (6) death. Animals exposed to distinct PTZ concentrations presented different seizure profiles, intensities and latencies to reach all scores. Only animals immersed into 15 mM PTZ showed an increased time to return to the normal behavior (score 0), after exposure. Total mortality rate at 10 and 15 mM were 33% and 50%, respectively. Considering all behavioral parameters, 5, 7.5, 10, and 15 mM PTZ, induced seizures with low, intermediate, and high severity, respectively. Pretreatment with diazepam (DZP) significantly attenuated seizure severity. Finally, the brain PTZ levels in adult zebrafish immersed into the chemoconvulsant solution at 5 and 10 mM were comparable to those described for the rodent model, with a peak after a 20-min of exposure. The PTZ brain levels observed after 2.5-min PTZ exposure and after 60-min removal from exposure were similar. Altogether, our results showed a detailed temporal behavioral characterization of a PTZ epileptic seizure model in adult zebrafish. These behavioral analyses and the simple method for PTZ quantification could be considered as important tools for future investigations and translational research.