Acute effects of amitriptyline on adult zebrafish: Potential relevance to antidepressant drug screening and modeling human toxidromes / Demin Konstantin A.,Kolesnikova Tatiana O.,Khatsko Sergey L.,Meshalkina Darya A.,Efimova Evgeniya V.,Morzherin Yuri Yu.,Kalueff Allan V. // NEUROTOXICOLOGY AND TERATOLOGY. - 2017. - V. 62, l. . - P. 27-33.

ISSN/EISSN:

0892-0362 / 1872-9738

Type:

Article

Abstract:

The need to develop novel antidepressants is an emerging problem in biomedicine. An aquatic vertebrate species, the zebrafish (Danio rerio) may serve as a useful in-vivo screen for CNS drugs, and displays high sensitivity to a wide range of antidepressants. Amitriptyline is a commonly used tricyclic antidepressant which acts primarily as a serotonin and noradrenaline reuptake inhibitor. Here, we characterize drug-induced behavioral and neurochemical responses in adult zebrafish following their acute exposure to amitriptyline. Overall, the drug at 1 and 5 mg/L significantly increased time spent in top and shortened the latency to enter it, thereby paralleling recent reports on zebrafish `serotonin toxicity-like behavior' caused by various serotonergic agents. The 10 mg/L dose of the drug also significantly decreased top entries and maximal velocity and evoked overt ataxia, likely due to emerging non-specific toxic effects. Amitriptyline at 5 and 10 mg/L also dose-dependently increased serotonin turnover, but not noradrenaline levels, in zebrafish whole-brain samples. Overall, zebrafish high sensitivity to acute effects of amitriptyline can help improve our understanding of psychopharmacological profiles of this compound and the related CNS drugs, and contributes further to the development of aquatic experimental models of human toxidromes.

Author keywords:

Zebrafish; Amitriptyline; Aquatic screening; Serotonin toxicity; Serotonin syndrome TRANSPORTER KNOCKOUT MICE; TANDEM MASS-SPECTROMETRY; SOLID-PHASE EXTRACTION; SEROTONIN SYNDROME; DIABETIC-NEUROPATHY; ANIMAL-MODEL; WASTE-WATER; ILLICIT DRUGS; BEHAVIOR; FLUOXETINE

DOI:

10.1016/j.ntt.2017.04.002

Web of Science ID:

ISI:000408300500004

Соавторы в МНС:

Другие поля

Поле	Значение
Month	JUL-AUG
Publisher	PERGAMON-ELSEVIER SCIENCE LTD
Address	THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
Language	English
EISSN	1872-9738
Keywords-Plus	TRANSPORTER KNOCKOUT MICE; TANDEM MASS-SPECTROMETRY; SOLID-PHASE EXTRACTION; SEROTONIN SYNDROME; DIABETIC-NEUROPATHY; ANIMAL-MODEL; WASTE-WATER; ILLICIT DRUGS; BEHAVIOR; FLUOXETINE
Research-Areas	Neurosciences \& Neurology; Toxicology
Web-of-Science-Categories	Neurosciences; Toxicology
Author-Email	avkalueff@gmail.com
Funding-Acknowledgement	Ural Federal University; St. Petersburg State University
Funding-Text	This study is dedicated to our co-author, Professor Yury Yu. Morzherin (1964-2017), who passed away suddenly after this manuscript was submitted. A good friend, trusted colleague, caring mentor and brilliant scientist, he will be sorely missed. The research was supported by Ural Federal University and St. Petersburg State University Intramural Research programs. Funders had no involvement in the study design, data collection or analysis, and MS preparation.
Number-of-Cited-References	73
Journal-ISO	Neurotoxicol. Teratol.
Doc-Delivery-Number	FE6DP