Antidepressant Screening Demonstrated Non-Monotonic Responses to Amitriptyline, Amoxapine and Sertraline in Locomotor Activity Assay in Larval Zebrafish

Antidepressants are well-known drugs to treat depression and major depressive disorder for humans. However, the misuse and abuse of antidepressants keep increasing with several side effects reported. The aim of this study was to assess the potential adverse effects of 18 antidepressants by monitorin...

Full description

Bibliographic Details
Main Authors: Michael Edbert Suryanto, Gilbert Audira, Boontida Uapipatanakul, Akhlaq Hussain, Ferry Saputra, Petrus Siregar, Kelvin H.-C. Chen, Chung-Der Hsiao
Format: Article
Language:English
Published: MDPI AG 2021-03-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/10/4/738
_version_ 1797539892530511872
author Michael Edbert Suryanto
Gilbert Audira
Boontida Uapipatanakul
Akhlaq Hussain
Ferry Saputra
Petrus Siregar
Kelvin H.-C. Chen
Chung-Der Hsiao
author_facet Michael Edbert Suryanto
Gilbert Audira
Boontida Uapipatanakul
Akhlaq Hussain
Ferry Saputra
Petrus Siregar
Kelvin H.-C. Chen
Chung-Der Hsiao
author_sort Michael Edbert Suryanto
collection DOAJ
description Antidepressants are well-known drugs to treat depression and major depressive disorder for humans. However, the misuse and abuse of antidepressants keep increasing with several side effects reported. The aim of this study was to assess the potential adverse effects of 18 antidepressants by monitoring zebrafish larval locomotor activity performance based on the total distance traveled, burst movement count, and total rotation count at four dark-light intercalated phases. In general, zebrafish larvae displayed sedative effects after antidepressant exposure by showing a significant reduction in all of the locomotor activity-related endpoints. However, three antidepressants i.e., amitriptyline, amoxapine, and sertraline were able to trigger a significantly high locomotor activity in zebrafish larvae during the light cycle. These differences might be due to the pharmacologic differences among the antidepressants. In addition, since each antidepressant possesses a different dosage range from the other, overdoses of these antidepressants might also be the causes of these differences. Furthermore, based on these results, a further study was conducted to observe the effect of these three antidepressants in lower concentrations. From the results, biphasic effects in terms of zebrafish larval locomotor activity were demonstrated by these drugs. Even though further studies are still required to validate the mechanism, these findings indicate that these antidepressants might share a common mechanism responsible for their effects on zebrafish larval locomotor activity although there were some differences in potency of these effects.
first_indexed 2024-03-10T12:51:16Z
format Article
id doaj.art-6af0c4b1049643689e984760bf9273b2
institution Directory Open Access Journal
issn 2073-4409
language English
last_indexed 2024-03-10T12:51:16Z
publishDate 2021-03-01
publisher MDPI AG
record_format Article
series Cells
spelling doaj.art-6af0c4b1049643689e984760bf9273b22023-11-21T13:00:14ZengMDPI AGCells2073-44092021-03-0110473810.3390/cells10040738Antidepressant Screening Demonstrated Non-Monotonic Responses to Amitriptyline, Amoxapine and Sertraline in Locomotor Activity Assay in Larval ZebrafishMichael Edbert Suryanto0Gilbert Audira1Boontida Uapipatanakul2Akhlaq Hussain3Ferry Saputra4Petrus Siregar5Kelvin H.-C. Chen6Chung-Der Hsiao7Department of Bioscience Technology, Chung Yuan Christian University, Chung-Li 320314, TaiwanDepartment of Bioscience Technology, Chung Yuan Christian University, Chung-Li 320314, TaiwanDepartment of Chemistry, Faculty of Science and Technology, Rajamangala University of Technology Thanyaburi, Thanyaburi 12110, ThailandDepartment of Bioscience Technology, Chung Yuan Christian University, Chung-Li 320314, TaiwanDepartment of Bioscience Technology, Chung Yuan Christian University, Chung-Li 320314, TaiwanDepartment of Bioscience Technology, Chung Yuan Christian University, Chung-Li 320314, TaiwanDepartment of Applied Chemistry, National Pingtung University, Pingtung 900391, TaiwanDepartment of Bioscience Technology, Chung Yuan Christian University, Chung-Li 320314, TaiwanAntidepressants are well-known drugs to treat depression and major depressive disorder for humans. However, the misuse and abuse of antidepressants keep increasing with several side effects reported. The aim of this study was to assess the potential adverse effects of 18 antidepressants by monitoring zebrafish larval locomotor activity performance based on the total distance traveled, burst movement count, and total rotation count at four dark-light intercalated phases. In general, zebrafish larvae displayed sedative effects after antidepressant exposure by showing a significant reduction in all of the locomotor activity-related endpoints. However, three antidepressants i.e., amitriptyline, amoxapine, and sertraline were able to trigger a significantly high locomotor activity in zebrafish larvae during the light cycle. These differences might be due to the pharmacologic differences among the antidepressants. In addition, since each antidepressant possesses a different dosage range from the other, overdoses of these antidepressants might also be the causes of these differences. Furthermore, based on these results, a further study was conducted to observe the effect of these three antidepressants in lower concentrations. From the results, biphasic effects in terms of zebrafish larval locomotor activity were demonstrated by these drugs. Even though further studies are still required to validate the mechanism, these findings indicate that these antidepressants might share a common mechanism responsible for their effects on zebrafish larval locomotor activity although there were some differences in potency of these effects.https://www.mdpi.com/2073-4409/10/4/738zebrafish larvaeantidepressantsbehaviorlocomotionphenomicsbiphasic effect
spellingShingle Michael Edbert Suryanto
Gilbert Audira
Boontida Uapipatanakul
Akhlaq Hussain
Ferry Saputra
Petrus Siregar
Kelvin H.-C. Chen
Chung-Der Hsiao
Antidepressant Screening Demonstrated Non-Monotonic Responses to Amitriptyline, Amoxapine and Sertraline in Locomotor Activity Assay in Larval Zebrafish
Cells
zebrafish larvae
antidepressants
behavior
locomotion
phenomics
biphasic effect
title Antidepressant Screening Demonstrated Non-Monotonic Responses to Amitriptyline, Amoxapine and Sertraline in Locomotor Activity Assay in Larval Zebrafish
title_full Antidepressant Screening Demonstrated Non-Monotonic Responses to Amitriptyline, Amoxapine and Sertraline in Locomotor Activity Assay in Larval Zebrafish
title_fullStr Antidepressant Screening Demonstrated Non-Monotonic Responses to Amitriptyline, Amoxapine and Sertraline in Locomotor Activity Assay in Larval Zebrafish
title_full_unstemmed Antidepressant Screening Demonstrated Non-Monotonic Responses to Amitriptyline, Amoxapine and Sertraline in Locomotor Activity Assay in Larval Zebrafish
title_short Antidepressant Screening Demonstrated Non-Monotonic Responses to Amitriptyline, Amoxapine and Sertraline in Locomotor Activity Assay in Larval Zebrafish
title_sort antidepressant screening demonstrated non monotonic responses to amitriptyline amoxapine and sertraline in locomotor activity assay in larval zebrafish
topic zebrafish larvae
antidepressants
behavior
locomotion
phenomics
biphasic effect
url https://www.mdpi.com/2073-4409/10/4/738
work_keys_str_mv AT michaeledbertsuryanto antidepressantscreeningdemonstratednonmonotonicresponsestoamitriptylineamoxapineandsertralineinlocomotoractivityassayinlarvalzebrafish
AT gilbertaudira antidepressantscreeningdemonstratednonmonotonicresponsestoamitriptylineamoxapineandsertralineinlocomotoractivityassayinlarvalzebrafish
AT boontidauapipatanakul antidepressantscreeningdemonstratednonmonotonicresponsestoamitriptylineamoxapineandsertralineinlocomotoractivityassayinlarvalzebrafish
AT akhlaqhussain antidepressantscreeningdemonstratednonmonotonicresponsestoamitriptylineamoxapineandsertralineinlocomotoractivityassayinlarvalzebrafish
AT ferrysaputra antidepressantscreeningdemonstratednonmonotonicresponsestoamitriptylineamoxapineandsertralineinlocomotoractivityassayinlarvalzebrafish
AT petrussiregar antidepressantscreeningdemonstratednonmonotonicresponsestoamitriptylineamoxapineandsertralineinlocomotoractivityassayinlarvalzebrafish
AT kelvinhcchen antidepressantscreeningdemonstratednonmonotonicresponsestoamitriptylineamoxapineandsertralineinlocomotoractivityassayinlarvalzebrafish
AT chungderhsiao antidepressantscreeningdemonstratednonmonotonicresponsestoamitriptylineamoxapineandsertralineinlocomotoractivityassayinlarvalzebrafish