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Behavioral effects of citalopram, tramadol, and binary mixture in zebrafish (Danio rerio) larvae
Swedish University of Agricultural Sciences.
Swedish University of Agricultural Sciences.
Södertörn University, School of Natural Sciences, Technology and Environmental Studies, Environmental Science.ORCID iD: 0000-0002-0856-9707
Swedish University of Agricultural Sciences.
2019 (English)In: Chemosphere, ISSN 0045-6535, E-ISSN 1879-1298, Vol. 238, article id 124587Article in journal (Refereed) Published
Abstract [en]

Pharmaceuticals are emerging as environmentally problematic compounds. As they are often not appropriately removed by sewage treatment plants, pharmaceutical compounds end up in surface water environments worldwide at concentrations in the ng to μg L−1 range. There is a need to further explore single compound and mixture effects using e.g. in vivo test model systems. We have investigated, for the first time, behavioral effects in larval zebrafish (Danio rerio) exposed to a binary mixture of an antidepressant drug (citalopram) and a synthetic opioid (tramadol). Citalopram and tramadol have a similar mode of action (serotonin reuptake inhibition) and are known to produce drug-drug interactional effects resulting in serotonin syndrome (SS) in humans. Zebrafish embryo-larvae were exposed to citalopram, tramadol and 1:1 binary mixture from fertilization until 144 h post fertilization. No effects on heart rate, spontaneous tail coiling, or death/malformations were observed in any treatment at tested concentrations. Behavior (hypoactivity in dark periods) was on the other hand affected, with lowest observed effect concentrations (LOECs) of 373 μg L−1 for citalopram, 320 μg L−1 for tramadol, and 473 μg L−1 for the 1:1 mixture. Behavioral EC50 was calculated to be 471 μg L−1 for citalopram, 411 μg L−1 for tramadol, and 713 μg L−1 for the 1:1 mixture. The results of this study conclude that tramadol and citalopram produce hypoactivity in 144 hpf zebrafish larvae. Further, a 1:1 binary mixture of the two caused the same response, albeit at a higher concentration, possibly due to SS.

Place, publisher, year, edition, pages
Elsevier, 2019. Vol. 238, article id 124587
Keywords [en]
Zebrafish embryotoxicity, 5-HT, SSRI, Synthetic opioid, Serotonin syndrome
National Category
Environmental Sciences
Research subject
Environmental Studies
Identifiers
URN: urn:nbn:se:sh:diva-38736DOI: 10.1016/j.chemosphere.2019.124587PubMedID: 31425864Scopus ID: 2-s2.0-85070565741OAI: oai:DiVA.org:sh-38736DiVA, id: diva2:1343186
Available from: 2019-08-15 Created: 2019-08-15 Last updated: 2019-08-23Bibliographically approved

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