Effects of a non-competitive N-methyl-d-aspartate (NMDA) antagonist, tiletamine, in adult zebrafish.

Autor: Kolesnikova TO; Ural Federal University, Ekaterinburg 620002, Russia., Khatsko SL; Ural Federal University, Ekaterinburg 620002, Russia., Shevyrin VA; Ural Federal University, Ekaterinburg 620002, Russia; Management of Federal Drug Control Service of Russia in Sverdlovsk Region, 31 Razin Str., Ekaterinburg 620142, Russia., Morzherin YY; Ural Federal University, Ekaterinburg 620002, Russia. Electronic address: yu.yu.morzherin@urfu.ru., Kalueff AV; Institute of Translational Biomedicine, St. Petersburg State University, St. Petersburg 199034, Russia. Electronic address: avkalueff@gmail.com.
Jazyk: angličtina
Zdroj: Neurotoxicology and teratology [Neurotoxicol Teratol] 2017 Jan - Feb; Vol. 59, pp. 62-67. Date of Electronic Publication: 2016 Dec 02.
DOI: 10.1016/j.ntt.2016.11.009
Abstrakt: Tiletamine is a non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist chemically related to ketamine and phencyclidine. A common veterinary anesthetic drug, tiletamine is currently a Schedule III controlled substance in USA. This compound exerts sedative effects in humans and animals, also having an abuse potential, toxicity and dissociative hallucinogenic properties clinically. However, the neurotropic profile of tiletamine remains poorly understood, necessitating novel models and in-vivo screens, including non-mammalian species. Zebrafish (Danio rerio) are rapidly becoming a popular model organism for screening various CNS drugs, including those acting at NMDA receptors. Here, we investigated acute behavioral effects of 1, 5 and 10mg/L of tiletamine on adult zebrafish. In the standard novel tank test, a 20-min immersion in 1mg/L of tiletamine produced no overt differences from control zebrafish (receiving 0.1% DMSO vehicle), except for reduced top entries. In contrast, tiletamine at 5 and 10mg/L exerted robust dose-dependent sedative effects in zebrafish (also darkening their skin coloration, similar to ketamine and PCP). Gas chromatography/mass spectrometry (GC/MS) analyses revealed no tiletamine peaks in control and 1mg/L groups, but detected tiletamine peaks in zebrafish brain samples at 5 and 10mg/L. Together, these findings demonstrate potent neurotropic effects of tiletamine in zebrafish, and their high sensitivity to this drug. Our findings also support the growing utility of fish-based aquatic screens for studying neuroactive properties of NMDA antagonists in-vivo.
(Copyright © 2016. Published by Elsevier Inc.)
Databáze: MEDLINE
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