Neurochemical Research

, Volume 43, Issue 6, pp 1191–1199 | Cite as

The Effects of Chronic Amitriptyline on Zebrafish Behavior and Monoamine Neurochemistry

  • Darya A. Meshalkina
  • Elana V. Kysil
  • Kristina A. Antonova
  • Konstantin A. Demin
  • Tatiana O. Kolesnikova
  • Sergey L. Khatsko
  • Raul R. Gainetdinov
  • Polina A. Alekseeva
  • Allan V. KalueffEmail author
Original Paper


Amitriptyline is a commonly used tricyclic antidepressant (TCA) inhibiting serotonin and norepinephrine reuptake. The exact CNS action of TCAs remains poorly understood, necessitating new screening approaches and novel model organisms. Zebrafish (Danio rerio) are rapidly emerging as a promising tool for pharmacological research of antidepressants, including amitriptyline. Here, we examine the effects of chronic 2-week exposure to 10 and 50 μg/L amitriptyline on zebrafish behavior and monoamine neurotransmitters. Overall, the drug at 50 μg/L evoked pronounced anxiolytic-like effects in the novel tank test (assessed by more time in top, fewer transition and shorter latency to enter the top). Like other TCAs, amitriptyline reduced serotonin turnover, but also significantly elevated whole-brain norepinephrine and dopamine levels. The latter effect was not reported in this model previously, and accompanied higher brain expression of tyrosine hydroxylase (a rate-limiting enzyme of catecholamine biosynthesis), but unaltered expression of dopamine-β-hydroxylase and monoamine oxidase (the enzymes of dopamine metabolism). This response may underlie chronic amitriptyline action on dopamine and norepinephrine neurotransmission, and contribute to the complex CNS profile of this drug observed both clinically and in animal models. Collectively, these findings also confirm the important role of monoamine modulation in the regulation of anxiety-related behavior in zebrafish, and support the utility of this organism as a promising in-vivo model for CNS drug screening.


Zebrafish Amitriptyline Tricyclic antidepressants Serotonin Dopamine Norephnephrine 



Laboratory zebrafish maintenance for this project was performed by the Environmental Safety Observatory Bioelectronic Complex of SPSU. The research was supported by the Russian Foundation for Basic Research (RFBR) grants 16-04-00851 to АVK, and 18-315-00375 to DAM. RRG was supported by a Russian Science Foundation (RSF) grant 14-50-00069.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Darya A. Meshalkina
    • 1
  • Elana V. Kysil
    • 1
  • Kristina A. Antonova
    • 1
  • Konstantin A. Demin
    • 1
    • 4
  • Tatiana O. Kolesnikova
    • 2
  • Sergey L. Khatsko
    • 2
  • Raul R. Gainetdinov
    • 1
    • 3
  • Polina A. Alekseeva
    • 4
  • Allan V. Kalueff
    • 5
    • 6
    • 7
    • 8
    • 9
    • 10
    • 11
    Email author
  1. 1.Institute of Translational BiomedicineSt. Petersburg UniversitySt. PetersburgRussia
  2. 2.Ural Federal UniversityEkaterinburgRussia
  3. 3.Skolkovo Institute of Science and TechnologySkoltechMoscowRussia
  4. 4.Institute of Experimental MedicineAlmazov National Medical Research CentreSt. PetersburgRussia
  5. 5.School of Pharmaceutical SciencesSouthwest UniversityChongqingChina
  6. 6.Laboratory of Biological Psychiatry, Institute of Translational BiomedicineSt. Petersburg UniversitySt. PetersburgRussia
  7. 7.Laboratory of PetrochemistryUral Federal UniversityEkaterinburgRussia
  8. 8.Almazov National Medical Research CentreSt. PetersburgRussia
  9. 9.Granov Russian National Research Center for Radiology and Surgical TechnologiesPesochnyRussia
  10. 10.ZENEREI Research CenterSlidellUSA
  11. 11.The International Zebrafish Neuroscience Research Consortium (ZNRC)SlidellUSA

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