Modeling psychiatric comorbid symptoms of epileptic seizures in zebrafish

Epilepsy is a debilitating neurological disorder characterized by recurrent unprovoked seizures. Anxiety, cognitive deficits, depressive-like symptoms, and social dysfunction are psychiatric comorbidities with high prevalence in epileptic patients. Due to the genetic and behavioral tractability, the zebrafish is a promising model organism to understand the neural bases involved in epilepsy-related comorbidities. Here, we aimed to characterize some behavioral phenotypes paralleling those observed in epilepsy-related comorbidities after a single pentylenetetrazole (PTZ) exposure in zebrafish. We also analyzed the influence of whole-body cortisol levels in the behavioral responses measured. Fish were exposed to 10 mM PTZ for 20 min to induce epileptic seizures. After 24 h recovery period, locomotion and anxiety-like responses (novel tank and light-dark tests), social interaction (shoaling behavior task), and memory retention (inhibitory avoidance protocol) were assessed. Basically, PTZ impaired habituation to novelty stress, evoked anxiogenic-like behaviors, disrupted shoaling, and caused memory consolidation deficits in zebrafish without changing whole-body cortisol levels. In conclusion, our novel findings further validate the use of zebrafish as a suitable tool for modeling epilepsy-related comorbidities in translational neuropsychiatric research.