Abstract
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.
Highlights
Epilepsy is a neurological disorder characterized by recurrent spontaneous epileptic seizures associated with distinct neurobiological and behavioral alterations [1]
Loscher et al [5], in a critical review about the current animal models of seizure and epilepsy employed to discovery and development of new antiepileptic drugs (AED), pointed out that this high refractoriness could be a result from using always the same proconvulsant focusing in rodent models
In the current study, we described a detailed behavioral characterization of the adult zebrafish epileptic seizure model induced by PTZ
Summary
Epilepsy is a neurological disorder characterized by recurrent spontaneous epileptic seizures associated with distinct neurobiological and behavioral alterations [1]. One of the methods used to investigate epileptic seizures in experimental models consists on the analysis of the behavioral profile through a seizure stage-score classification [2] This characterization is well established in rodents for seizures induced by electrical kindling Racine et al [3] and for chemoconvulsant drugs, such as kainate (KA), pilocarpine and pentylenetetrazole (PTZ) [4]. Exposure to PTZ induces a concentration-dependent sequence of stereotyped behavioral changes that starts with orofacial movements and culminates in clonus-like seizures in rodent models This seizure model has been widely used in the past 6 decades for discovery and development of several antiepileptic drugs (AED), such as benzodiazepines, valproate, gabapentine, etc [5,6,7]. Loscher et al [5], in a critical review about the current animal models of seizure and epilepsy employed to discovery and development of new AED, pointed out that this high refractoriness could be a result from using always the same proconvulsant focusing in rodent models
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