Pharmacological Modulation of Serotonin Levels in Zebrafish Larvae: Lessons for Identifying Environmental Neurotoxicants Targeting the Serotonergic System
This study examines the effects of acute pharmacological modulation of the serotonergic system over zebrafish larvae’s cognitive, basic, and defense locomotor behaviors, using a medium to high throughput screening assay. Furthermore, the relationship between behavior, enzyme activity related to neur...
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doaj-753107463ab345658cb39ab1f81be1102021-06-01T01:05:31ZengMDPI AGToxics2305-63042021-05-01911811810.3390/toxics9060118Pharmacological Modulation of Serotonin Levels in Zebrafish Larvae: Lessons for Identifying Environmental Neurotoxicants Targeting the Serotonergic SystemMelissa Faria0Eva Prats1Marina Bellot2Cristian Gomez-Canela3Demetrio Raldúa4Institute for Environmental Assessment and Water Research (IDAEA-CSIC), Jordi Girona 18, 08034 Barcelona, SpainResearch and Development Centre (CID-CSIC), Jordi Girona 18, 08034 Barcelona, SpainDepartment of Analytical Chemistry and Applied (Chromatography Section), School of Engineering, Institut Químic de Sarrià-Universitat Ramon Llull, Via Augusta 390, 08017 Barcelona, SpainDepartment of Analytical Chemistry and Applied (Chromatography Section), School of Engineering, Institut Químic de Sarrià-Universitat Ramon Llull, Via Augusta 390, 08017 Barcelona, SpainInstitute for Environmental Assessment and Water Research (IDAEA-CSIC), Jordi Girona 18, 08034 Barcelona, SpainThis study examines the effects of acute pharmacological modulation of the serotonergic system over zebrafish larvae’s cognitive, basic, and defense locomotor behaviors, using a medium to high throughput screening assay. Furthermore, the relationship between behavior, enzyme activity related to neurotransmitter metabolism, neurotransmitter levels, and gene expression was also determined. Modulation of larvae serotonergic system was accomplished by 24 h exposure to single and opposite pharmacodynamics co-exposure to three model psychopharmaceuticals with antagonistic and agonistic serotonin signaling properties: 2.5 mM 4-Chloro-DL-phenylalanine (PCPA) and 5 µM deprenyl and 0.5 µM fluoxetine, respectively. Similar behavioral outcome was observed for deprenyl and fluoxetine, which was reflected as hypolocomotion, decrease in larvae defensive responses, and cognitive impairment. Contrarily, PCPA induced hyperlocomotion and increase in larvae escape response. Deprenyl exposure effects were more pronounced at a lower level of organization than fluoxetine, with complete inhibition of monoamine oxidase (MAO) activity, dramatic increase of 5-HT and dopamine (DA) levels, and downregulation of serotonin synthesis and transporter genes. PCPA showed mainly effects over serotonin and dopamine’s main degradation metabolites. Finally, co-exposure between agonistic and antagonist serotonin signaling drugs reviled full recovery of zebrafish impaired locomotor and defense responses, 5-HT synthesis gene expression, and partial recovery of 5-HT levels. The findings of this study suggest that zebrafish larvae can be highly sensitive and a useful vertebrate model for short-term exposure to serotonin signaling changes.https://www.mdpi.com/2305-6304/9/6/118zebrafish larvaebehaviorserotoninneurotransmittersmodulation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Melissa Faria Eva Prats Marina Bellot Cristian Gomez-Canela Demetrio Raldúa |
spellingShingle |
Melissa Faria Eva Prats Marina Bellot Cristian Gomez-Canela Demetrio Raldúa Pharmacological Modulation of Serotonin Levels in Zebrafish Larvae: Lessons for Identifying Environmental Neurotoxicants Targeting the Serotonergic System Toxics zebrafish larvae behavior serotonin neurotransmitters modulation |
author_facet |
Melissa Faria Eva Prats Marina Bellot Cristian Gomez-Canela Demetrio Raldúa |
author_sort |
Melissa Faria |
title |
Pharmacological Modulation of Serotonin Levels in Zebrafish Larvae: Lessons for Identifying Environmental Neurotoxicants Targeting the Serotonergic System |
title_short |
Pharmacological Modulation of Serotonin Levels in Zebrafish Larvae: Lessons for Identifying Environmental Neurotoxicants Targeting the Serotonergic System |
title_full |
Pharmacological Modulation of Serotonin Levels in Zebrafish Larvae: Lessons for Identifying Environmental Neurotoxicants Targeting the Serotonergic System |
title_fullStr |
Pharmacological Modulation of Serotonin Levels in Zebrafish Larvae: Lessons for Identifying Environmental Neurotoxicants Targeting the Serotonergic System |
title_full_unstemmed |
Pharmacological Modulation of Serotonin Levels in Zebrafish Larvae: Lessons for Identifying Environmental Neurotoxicants Targeting the Serotonergic System |
title_sort |
pharmacological modulation of serotonin levels in zebrafish larvae: lessons for identifying environmental neurotoxicants targeting the serotonergic system |
publisher |
MDPI AG |
series |
Toxics |
issn |
2305-6304 |
publishDate |
2021-05-01 |
description |
This study examines the effects of acute pharmacological modulation of the serotonergic system over zebrafish larvae’s cognitive, basic, and defense locomotor behaviors, using a medium to high throughput screening assay. Furthermore, the relationship between behavior, enzyme activity related to neurotransmitter metabolism, neurotransmitter levels, and gene expression was also determined. Modulation of larvae serotonergic system was accomplished by 24 h exposure to single and opposite pharmacodynamics co-exposure to three model psychopharmaceuticals with antagonistic and agonistic serotonin signaling properties: 2.5 mM 4-Chloro-DL-phenylalanine (PCPA) and 5 µM deprenyl and 0.5 µM fluoxetine, respectively. Similar behavioral outcome was observed for deprenyl and fluoxetine, which was reflected as hypolocomotion, decrease in larvae defensive responses, and cognitive impairment. Contrarily, PCPA induced hyperlocomotion and increase in larvae escape response. Deprenyl exposure effects were more pronounced at a lower level of organization than fluoxetine, with complete inhibition of monoamine oxidase (MAO) activity, dramatic increase of 5-HT and dopamine (DA) levels, and downregulation of serotonin synthesis and transporter genes. PCPA showed mainly effects over serotonin and dopamine’s main degradation metabolites. Finally, co-exposure between agonistic and antagonist serotonin signaling drugs reviled full recovery of zebrafish impaired locomotor and defense responses, 5-HT synthesis gene expression, and partial recovery of 5-HT levels. The findings of this study suggest that zebrafish larvae can be highly sensitive and a useful vertebrate model for short-term exposure to serotonin signaling changes. |
topic |
zebrafish larvae behavior serotonin neurotransmitters modulation |
url |
https://www.mdpi.com/2305-6304/9/6/118 |
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