{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T22:37:47Z","timestamp":1776206267424,"version":"3.50.1"},"reference-count":65,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,1,29]],"date-time":"2022-01-29T00:00:00Z","timestamp":1643414400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","award":["REWATER (ERA-NET Cofund WaterWorks2015, Water JPI)"],"award-info":[{"award-number":["REWATER (ERA-NET Cofund WaterWorks2015, Water JPI)"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","award":["PSYCHOBASS (PTDC\/AAG MAA\/2405\/2012)"],"award-info":[{"award-number":["PSYCHOBASS (PTDC\/AAG MAA\/2405\/2012)"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","award":["UIDB\/04423\/2020"],"award-info":[{"award-number":["UIDB\/04423\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","award":["UIDP\/04423\/2020"],"award-info":[{"award-number":["UIDP\/04423\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","award":["SRFH\/BD\/134518\/2017"],"award-info":[{"award-number":["SRFH\/BD\/134518\/2017"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Water"],"abstract":"<jats:p>The occurrence of psychopharmaceuticals in aquatic ecosystems is a growing problem. Fluoxetine (FL) and its metabolite norfluoxetine (NF) are selective serotonin reuptake inhibitors. Although they may be potentially harmful to non-target species, available knowledge on the effects of NF is sparse, relative to FL. This study aimed at contributing to the body of knowledge about the modes-of-action (MoA) of these compounds and their underlying mechanisms eliciting hazardous effects during the early development of the teleost model zebrafish (Danio rerio). One hour post-fertilisation (hpf), embryos were exposed up to 80 hpf to these compounds at levels found in surface waters and higher (FL, 0.0015 and 0.05 \u00b5M; NF, 0.00006 and 0.0014 \u00b5M). Developmental anomalies were observed at 8, 32 and 80 hpf. Larvae were collected at 80 hpf to assess the expression of 34 genes related to FL and NF MoA and metabolism, using qPCR (quantitative reverse transcription PCR). Results showed that both compounds elicited an increased frequency of embryos exhibiting abnormal pigmentation, relative to controls. Gene expression alterations were more pronounced in FL- than in NF-exposed larvae. Cluster Analysis revealed two groups of genes discriminating between the drugs. for their marked opposing responses. Globally, downregulation of gene expression was typical of FL, whilst upregulation or no alteration was found for NF. These clusters identified were linked to the adrenergic pathway and to the retinoid and peroxisome proliferator-activated nuclear receptors. Overall, our data contradict the prevailing notion that NF is more toxic than FL and unveiled the expression levels of genes drd2b, 5-ht2c and abcc2 as possible markers of exposure to FL.<\/jats:p>","DOI":"10.3390\/w14030417","type":"journal-article","created":{"date-parts":[[2022,1,30]],"date-time":"2022-01-30T00:12:56Z","timestamp":1643501576000},"page":"417","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Differential Molecular Responses of Zebrafish Larvae to Fluoxetine and Norfluoxetine"],"prefix":"10.3390","volume":"14","author":[{"given":"Pedro","family":"Rodrigues","sequence":"first","affiliation":[{"name":"Interdisciplinary Centre of Marine and Environmental Research, University of Porto, Terminal de Cruzeiros do Porto de Leix\u00f5es Av. General Norton de Matos s\/n, 4450-208 Matosinhos, Portugal"},{"name":"Institute of Biomedical Sciences Abel Salazar, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal"},{"name":"Biology Department, Faculty of Sciences, Rua do Campo Alegre s\/n, University of Porto, 4169-007 Porto, Portugal"}]},{"given":"Virg\u00ednia","family":"Cunha","sequence":"additional","affiliation":[{"name":"Interdisciplinary Centre of Marine and Environmental Research, University of Porto, Terminal de Cruzeiros do Porto de Leix\u00f5es Av. General Norton de Matos s\/n, 4450-208 Matosinhos, Portugal"}]},{"given":"Marta","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Interdisciplinary Centre of Marine and Environmental Research, University of Porto, Terminal de Cruzeiros do Porto de Leix\u00f5es Av. General Norton de Matos s\/n, 4450-208 Matosinhos, Portugal"},{"name":"School of Marine Studies, Faculty of Science, Technology and Environment, The University of South Pacific, Laucala Bay Road, Suva VF23 + 49, Fiji"}]},{"given":"Maria Armanda","family":"Reis-Henriques","sequence":"additional","affiliation":[{"name":"Interdisciplinary Centre of Marine and Environmental Research, University of Porto, Terminal de Cruzeiros do Porto de Leix\u00f5es Av. General Norton de Matos s\/n, 4450-208 Matosinhos, Portugal"},{"name":"Institute of Biomedical Sciences Abel Salazar, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal"}]},{"given":"Lu\u00eds","family":"Oliva-Teles","sequence":"additional","affiliation":[{"name":"Interdisciplinary Centre of Marine and Environmental Research, University of Porto, Terminal de Cruzeiros do Porto de Leix\u00f5es Av. General Norton de Matos s\/n, 4450-208 Matosinhos, Portugal"},{"name":"Biology Department, Faculty of Sciences, Rua do Campo Alegre s\/n, University of Porto, 4169-007 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3360-3783","authenticated-orcid":false,"given":"Laura","family":"Guimar\u00e3es","sequence":"additional","affiliation":[{"name":"Interdisciplinary Centre of Marine and Environmental Research, University of Porto, Terminal de Cruzeiros do Porto de Leix\u00f5es Av. General Norton de Matos s\/n, 4450-208 Matosinhos, Portugal"}]},{"given":"Ant\u00f3nio Paulo","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Interdisciplinary Centre of Marine and Environmental Research, University of Porto, Terminal de Cruzeiros do Porto de Leix\u00f5es Av. General Norton de Matos s\/n, 4450-208 Matosinhos, Portugal"},{"name":"Biology Department, Faculty of Sciences, Rua do Campo Alegre s\/n, University of Porto, 4169-007 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1700","DOI":"10.1016\/S0140-6736(21)02143-7","article-title":"Global prevalence and burden of depressive and anxiety disorders in 204 countries and territories in 2020 due to the COVID-19 pandemic","volume":"398","author":"Santomauro","year":"2021","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"150846","DOI":"10.1016\/j.scitotenv.2021.150846","article-title":"Proximate causes and ultimate effects of common antidepressants, fluoxetine and venlafaxine, on fish behavior","volume":"807","author":"Salahinejad","year":"2021","journal-title":"Sci. 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