Effects of new antiseizure drugs on seizure activity and anxiety-like behavior in adult zebrafish.

Abstract

Several studies with larvae and adult zebrafish have shown that old and new antiseizure drugs (ASDs) produce discrepant results in seizure tests, locomotor activity or anxiety models. In this study, the pentylenetetrazole seizure test (PTZ) was performed to assess the effectiveness of four new ASDs: lamotrigine (LTG), topiramate (TPM), felbamate (FBM), and levetiracetam (LEV) in the subsequent stages of seizures in adult fish. All ASDs were administered intraperitoneally (i.p.). The time of maximal anticonvulsant effect and the dose-response relationship of the drugs were assessed. The effects of studied ASDs on the locomotor activity and the anxiety-like behavior in the color preference test were also investigated. Furthermore, drug concentrations in zebrafish homogenates were determined. LTG, TPM, and LEV significantly increased the seizure latency at three subsequent stages of seizures (SI-SIII), while FBM was effective only at SI. Locomotor activity decreased after TPM treatment. TPM and FBM exhibited a strong anxiolytic-like effect in the color preference test. LEV at the highest dose tested had a weak anxiolytic-like effect. The HPLC analysis showed average concentrations of the studied ASDs in the fish body during their maximum anticonvulsant activity. The present study shows that FBM cannot inhibit all subsequent PTZ seizure stages in the adult fish. Except for LTG, the studied drugs affected the anxiety-like behavior of treated animals. Furthermore, only TPM significantly changed locomotion parameters. Our findings support the need to accurately characterize the efficacy of new ASDs at different stages of the PTZ-induced seizures in adult zebrafish.

• Authors: Mateusz Pieróg, Katarzyna Socała, Urszula Doboszewska, Elżbieta Wyska, Leszek Guz, Aleksandra Szopa, Anna Serefko, Ewa Poleszak, Piotr Wlaź
• Journal: Toxicology and applied pharmacology (Toxicol Appl Pharmacol) Vol. 427 Pg. 115655 (09 15 2021) ISSN: 1096-0333 [Electronic] United States
• PMID: 34329640 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.

Chemical References

• Anti-Anxiety Agents
• Anticonvulsants
• Topiramate
• Levetiracetam
• Lamotrigine
• Pentylenetetrazole
• Felbamate

Topics

• Age Factors
• Animals
• Anti-Anxiety Agents (pharmacology, therapeutic use)
• Anticonvulsants (pharmacology, therapeutic use)
• Anxiety (drug therapy, psychology)
• Dose-Response Relationship, Drug
• Felbamate (pharmacology, therapeutic use)
• Female
• Lamotrigine (pharmacology, therapeutic use)
• Levetiracetam (pharmacology, therapeutic use)
• Locomotion (drug effects, physiology)
• Male
• Pentylenetetrazole (toxicity)
• Seizures (chemically induced, drug therapy, psychology)
• Topiramate (pharmacology, therapeutic use)
• Zebrafish