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Authors & Affiliations
Kazuo Okanari, Hitoshi Teranishi, Ryohei Umeda, Kenshiro Shikano, Masanori Inoue, Toshikatsu Hanada, Kenji Ihara, Reiko Hanada
Abstract
【Aims】Epilepsy, a recurrent neurological disease with abnormal neurotransmitter kinetics in the brain, has emerged as a global health concern. The mechanism of epileptic seizures is thought to involve a relative imbalance between excitatory and inhibitory neurotransmitters. Despite the recent advances in clinical and basic research on the pathogenesis of epilepsy, the complex relationship between the neurotransmitter dynamics and behavior with and without antiepileptic drugs (AEDs) during seizures remains unclear. We aimed to investigate the dynamics of neurotransmitters during convulsive seizures with and without treatment.【Methods】To investigate the effects of AEDs such as levetiracetam (LEV), carbamazepine (CBZ), and fenfluramine (FFR) on the major neurotransmitters in the pentylenetetrazol (PTZ)-induced seizures in adult zebrafish, we examined the changes of glutamic acid, gamma-aminobutyric acid (GABA), serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), choline, acetylcholine, norepinephrine, dopamine (DA), 3,4-Dihydroxyphenylacetic acid (DOPAC), and adenosine. 【Results】In this study, we observed that 5-HT and DA levels in the brain increased immediately after PTZ-induced seizures. Behavioral tests clearly showed that all of these AEDs suppressed the PTZinduced seizures. Upon treatment of PTZ-induced seizures with these AEDs, CBZ decreased the glutamic acid and FFR increased the GABA levels; however, no alternation of neurotransmitters in the brain was observed with LEV administration. 【Conclusions】We identified unique neurotransmitter changes of AEDs, such as LEV, CBZ, and FFR under PTZ-induced seizure conditions. These findings contribute to a better understanding of the pathophysiological aspects of epileptic seizures.