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 Kalueff

Результат исследований: Научные публикации в периодических изданияхстатья

5 Цитирования (Scopus)

Выдержка

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.
Язык оригиналаанглийский
Страницы (с-по)1191-1199
Число страниц9
ЖурналNeurochemical Research
Том43
Номер выпуска6
Ранняя дата в режиме онлайн2018
DOI
СостояниеОпубликовано - июн 2018

Отпечаток

Neurochemistry
Amitriptyline
Zebrafish
Dopamine
Norepinephrine
Brain
Serotonin
Screening
Pharmaceutical Preparations
Preclinical Drug Evaluations
Tricyclic Antidepressive Agents
Biosynthesis
Anti-Anxiety Agents
Monoamine Oxidase
Tyrosine 3-Monooxygenase
Enzymes
Mixed Function Oxygenases
Metabolism
Synaptic Transmission
Antidepressive Agents

Предметные области Scopus

  • Биохимия
  • Клеточная и молекулрная нейробиология

Цитировать

Meshalkina, D. A., Kysil, E. V., Antonova, K. A., Demin, K. A., Kolesnikova, T. O., Khatsko, S. L., ... Kalueff, A. V. (2018). The Effects of Chronic Amitriptyline on Zebrafish Behavior and Monoamine Neurochemistry. Neurochemical Research, 43(6), 1191-1199. https://doi.org/10.1007/s11064-018-2536-5
Meshalkina, Darya A ; Kysil, Elana V ; Antonova, Kristina A ; Demin, Konstantin A ; Kolesnikova, Tatiana O ; Khatsko, Sergey L ; Gainetdinov, Raul R ; Alekseeva, Polina A ; Kalueff, Allan V. / The Effects of Chronic Amitriptyline on Zebrafish Behavior and Monoamine Neurochemistry. В: Neurochemical Research. 2018 ; Том 43, № 6. стр. 1191-1199.
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abstract = "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.",
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Meshalkina, DA, Kysil, EV, Antonova, KA, Demin, KA, Kolesnikova, TO, Khatsko, SL, Gainetdinov, RR, Alekseeva, PA & Kalueff, AV 2018, 'The Effects of Chronic Amitriptyline on Zebrafish Behavior and Monoamine Neurochemistry', Neurochemical Research, том. 43, № 6, стр. 1191-1199. https://doi.org/10.1007/s11064-018-2536-5

The Effects of Chronic Amitriptyline on Zebrafish Behavior and Monoamine Neurochemistry. / Meshalkina, Darya A; Kysil, Elana V; Antonova, Kristina A; Demin, Konstantin A; Kolesnikova, Tatiana O; Khatsko, Sergey L; Gainetdinov, Raul R; Alekseeva, Polina A; Kalueff, Allan V.

В: Neurochemical Research, Том 43, № 6, 06.2018, стр. 1191-1199.

Результат исследований: Научные публикации в периодических изданияхстатья

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T1 - The Effects of Chronic Amitriptyline on Zebrafish Behavior and Monoamine Neurochemistry

AU - Meshalkina, Darya A

AU - Kysil, Elana V

AU - Antonova, Kristina A

AU - Demin, Konstantin A

AU - Kolesnikova, Tatiana O

AU - Khatsko, Sergey L

AU - Gainetdinov, Raul R

AU - Alekseeva, Polina A

AU - Kalueff, Allan V

PY - 2018/6

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N2 - 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.

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