Oral diazepam suppresses pentylenetetrazole-induced seizure-like behavior in adult zebrafish: A tool for nonclinical studies

Abstract

Epilepsy is one of the most severe and common neurologic disorders, affecting more than 50 million people worldwide. This disturbance is characterized by spontaneous and recurrent convulsions due to abnormal, excessive, and synchronous electrical triggers in the neural network. This study aimed to describe the behavior analysis of epileptic behavior in adult zebrafish induced by intraperitoneal (ip) pentylenetetrazole (PTZ) and the effects of oral (po) diazepam (DZP) on it. Animals’ behavior was recorded for 20 minutes after treatment with saline solution (vehicle), PTZ (125/250/400/500 mg/kg), or cotreatment with DZP (10 mg/kg) + PTZ (250/400 mg/kg). Then, altered behavioral manifestation was scored between 0 and 6 according to the following parameters: seizure score and cumulative frequency, seizure intensity measured through the area under the curve, clonic seizure latency, tonic seizure latency, and survival rate. The control group had scores between 0 and 3 and smaller convulsion intensity when compared to the PTZ-treated group. This latter group’s scores ranged from 0 to 6. Moreover, the convulsion intensity ranged from the median (PTZ at 125 mg/kg) to high (PTZ at 250/400/500 mg/kg). The latency to score 4 was similar in all PTZ treatments. However, latency to score 5 was higher in groups treated with PTZ at 400 and 500 mg/kg and was not detected in the group treated with PTZ at 125 mg/kg. Cotreatment with DZP + PTZ had scores between 0 and 5, less convulsion intensity, and higher latency to scores 4 and 5. Animals’ death occurred only in the group treated with PTZ at 500 mg/kg. These results show behavioral characterization of seizure scores in zebrafish treated with PTZ (ip) and DZP (po). This is a valuable tool for translational research and a more feasible model to replicate data in mammals.