Effects of a non-competitive N-methyl-D-aspartate (NMDA) antagonist, tiletamine, in adult zebrafish / Kolesnikova Tatiana O.,Khatsko Sergey L.,Shevyrin Vadim A.,Morzherin Yuri Yu,Kalueff Allan V. // NEUROTOXICOLOGY AND TERATOLOGY. - 2017. - V. 59, l. . - P. 62-67.

ISSN/EISSN:

0892-0362 / 1872-9738

Type:

Article

Abstract:

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 10 mg/L of tiletamine on adult zebrafish. In the standard novel tank test, a 20-min immersion in 1 mg/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 10 mg/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 1 mg/L groups, but detected tiletamine peaks in zebrafish brain samples at 5 and 10 mg/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. (C) 2016 Published by Elsevier Inc.

Author keywords:

Zebrafish; Tiletamine; Aquatic screening; Sedative effects; Central glutamatergic system; Ketamine HCL CI-634; BENZODIAZEPINE COMBINATION; DEVELOPING UTILITY; ZOLAZEPAM; PHENCYCLIDINE; EXPOSURE; MODELS; DRUGS; KETAMINE; BINDING

DOI:

10.1016/j.ntt.2016.11.009

Web of Science ID:

ISI:000392890100007

Соавторы в МНС:

Другие поля

Поле	Значение
Month	JAN-FEB
Publisher	PERGAMON-ELSEVIER SCIENCE LTD
Address	THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
Language	English
EISSN	1872-9738
Keywords-Plus	HCL CI-634; BENZODIAZEPINE COMBINATION; DEVELOPING UTILITY; ZOLAZEPAM; PHENCYCLIDINE; EXPOSURE; MODELS; DRUGS; KETAMINE; BINDING
Research-Areas	Neurosciences \& Neurology; Toxicology
Web-of-Science-Categories	Neurosciences; Toxicology
Author-Email	yu.yu.morzherin@urfu.su avkalueff@gmail.com
ResearcherID-Numbers	Khatsko, Sergey/E-3215-2017 Kolesnikova, Tatiana/E-3292-2017 Shevyrin, Vadim/F-2416-2017
ORCID-Numbers	Khatsko, Sergey/0000-0001-5921-6680 Kolesnikova, Tatiana/0000-0002-5561-8583 Shevyrin, Vadim/0000-0002-0369-0786
Funding-Acknowledgement	Ural Federal University Intramural Research program
Funding-Text	This study was supported by Ural Federal University Intramural Research program. Funders had no involvement in the study design, data collection or analysis, and MS preparation.
Number-of-Cited-References	30
Usage-Count-Last-180-days	4
Usage-Count-Since-2013	4
Journal-ISO	Neurotoxicol. Teratol.
Doc-Delivery-Number	EJ0HV