sh.sePublications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Waterborne citalopram has anxiolytic effects and increases locomotor activity in the three-spine stickleback (Gasterosteus aculeatus)
Södertörn University, School of Natural Sciences, Technology and Environmental Studies, Environmental Science.
Södertörn University, School of Natural Sciences, Technology and Environmental Studies, Environmental Science.
Uppsala University.
Södertörn University, School of Natural Sciences, Technology and Environmental Studies, Biology.ORCID iD: 0000-0001-9498-3033
Show others and affiliations
2016 (English)In: Aquatic Toxicology, ISSN 0166-445X, E-ISSN 1879-1514, Vol. 173, 19-28 p.Article in journal (Refereed) Published
Abstract [en]

Citalopram is an antidepressant drug, which acts by inhibiting the re-uptake of serotonin from the synaptic cleft into the pre-synaptic nerve ending. It is one of the most common drugs used in treatment of depression, it is highly lipophilic and frequently found in sewage treatment plant effluents and surface waters around the world. Citalopram and other selective serotonin re-uptake inhibitors have, at concentrations that occur in nature, been shown to have behavioural as well as physiological effects on fish and other animals. This study is the result of several different experiments, intended to analyse different aspects of behavioural effects of chronic citalopram exposure in fish. Our model species the three-spine stickleback is common in the entire northern hemisphere and is considered to be a good environmental sentinel species. Female three-spine sticklebacks were exposed to 0, 1.5 and 15μg/l nominal concentrations of citalopram for 21 days and subjected to the novel tank (NT) diving test. In the NT test, the fish exposed to 1.5μg/l, but not the 15μg/l fish made a significantly higher number of transitions to the upper half and stayed there for significantly longer time than the fish exposed to 0μg/l. The 15μg/l group, however, displayed a significantly lower number of freeze bouts and a shorter total freezing time. The test for locomotor activity included in the NT test showed that fish treated with 1.5 and 15μg/l displayed a significantly higher swimming activity than control fish both 5-7 and 15-17min after the start of the experiment. In the next experiment we compared fish exposed to 1.5μg/l and 0.15μg/l to pure water controls with regard to shoaling intensity and found no effect of treatment. In the final experiment the propensity of fish treated with 1.5μg/l to approach an unknown object and aggressive behaviour was investigated using the Novel Object test and a mirror test, respectively. The exposed fish ventured close to the unknown object significantly more often and stayed there for significantly longer time than unexposed fish. The aggression test yielded no statistically significant effects. It is concluded that citalopram changes the behaviour of the three-spine stickleback in a way that is likely to have ecological consequences and that it must not be considered an environmentally safe pharmaceutical.

Place, publisher, year, edition, pages
2016. Vol. 173, 19-28 p.
Keyword [en]
Call centre, identity, membership categorization analysis (MCA), multilingualism, omnirelevance, outsourcing, relational talk, transactional talk
National Category
Environmental Sciences Biological Sciences
Research subject
Environmental Studies; Baltic and East European studies
Identifiers
URN: urn:nbn:se:sh:diva-29453DOI: 10.1016/j.aquatox.2015.12.026ISI: 000372689900003PubMedID: 26827268Scopus ID: 2-s2.0-84955596941OAI: oai:DiVA.org:sh-29453DiVA: diva2:900962
Funder
The Foundation for Baltic and East European StudiesStockholm County Council
Available from: 2016-02-05 Created: 2016-02-05 Last updated: 2017-04-19Bibliographically approved
In thesis
1. Selective serotonin re-uptake inhibitors in the environment: Effects of citalopram on fish behaviour
Open this publication in new window or tab >>Selective serotonin re-uptake inhibitors in the environment: Effects of citalopram on fish behaviour
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Selective serotonin re-uptake inhibitors (SSRIs) are a class of anxiolytic and anti-depressant drugs. SSRIs act on the evolutionarily ancient serotonergic system which is virtually identical throughout the vertebrate phylum. Serotonin is involved in a wide range of processes ranging from neuronal and craniofacial embryonic development to regulation of behaviour. However, SSRIs are also emerging pollutants, mainly entering the environment via sewage treatment plants. Since the serotonergic system is virtually identical in humans and other animals, exposed animals will be affected in similar ways as humans and suspicions are rising that ecologically important behaviours may be affected in subtle ways. Using the three-spined stickleback (Gasterosteus aculeatus) and zebrafish (Danio rerio) as model organisms, this thesis focuses on the behavioural effects of SSRIs in fish. The SSRI used throughout this thesis is citalopram, which has been found in fish in coastal areas of the Baltic Sea and other parts of the world.

Effects on behaviour were investigated using several different tests measuring stress response, feeding behaviour, aggression and locomotor activity. Anxiolytic effects of 0.1 μg/l, 1.5 μg/l 15 μg/l were investigated as well as effects of 0.15 μg/l and 1.5 μg/l on feeding behaviour. Because serotonin is involved in the development of the nervous system, the effects of developmental exposure to 1.5 μg/l was studied after 100 days of remediation. Finally, because SSRIs rarely occur alone in natural waters, the effects on zebrafish of citalopram in a cocktail scenario, with the anxiogenic compound 17α-ethinyl estradiol (EE2 ) was also investigated. Citalopram was found to have anxiolytic effects on the three-spined stickleback at 0.1 μg/l, 1.5 μg/l and 15 μg/l.

Citalopram also suppressed feeding behaviour within a week of exposure and at concentrations as low as 0.15 μg/l. Developmental exposure to 1.5 μg/l for 30 days was found to increase aggression and feeding behaviour and to reduce locomotor activity. The changes were persistent and remained in adult fish. In the cocktail scenario, citalopram in single-substance exposure had anxiolytic effects on one parameter in the novel tank test at 0.1 μg/l. Citalopram enhanced the anxiogenic effects of EE2 in the novel tank test, but in the scototaxis test citalopram appeared to counteract the effects of EE2. It is concluded that citalopram has the potential to affect behaviour in fish at concentrations that have been found in close proximity of sewage treatment plants.

Abstract [sv]

Det serotonerga systemet är i stort sett identiskt hos människor och övriga vertebrater. Serotonin är inblandat i ett stort antal kroppsliga funktioner, bland annat stressreaktioner, reglering av födobeteende och aggression. Vidare är serotonin med och reglerar nervsystemets tillväxt under embryonalutvecklingen. Selektiva serotoninåterupptagshämmare (SSRI) är en grupp antidepressiva och lugnande läkemedel vars användning har ökat snabbt på senare år då de är effektiva och har få allvarliga bieffekter. SSRI verkar på det serotonerga systemet, genom att blockera återupptaget av serotonin i den presynaptiska nervänden. SSRI har tilldragit sig en viss uppmärksamhet som potentiella miljöhot då de visats kunna påverka ekologiskt relevanta beteenden hos fisk och andra akvatiska organismer vid relativt låga koncentrationer i miljön samtidigt som de bryts ned dåligt i avloppsreningsverk. Avhandlingen fokuserar på ekologiskt relevanta beteendeeffekter av SSRI på fisk, med storspigg (Gasterosteus aculeatus) och zebrafisk (Danio rerio) som modellorganismer. Citalopram har använts som försökssubstans då det anses vara den SSRI som har minst antal sidoeffekter på till exempel det dopaminerga systemet. Citalopram förekommer i utloppsvatten från reningsverk i alla industrialiserade länder och har även hittats i abborre i Östersjön.

Effekter av exponering för SSRI har påvisats med hjälp av olika beteendetest. Skototaxi-test och novel tank diving test mäter stressresponsen genom att kvantifiera preferensen för närhet till botten och mörka omgivningar. Ätbeteende har mätts som antal utfall mot en matbit under en given tidsperiod och aggression har mätts genom att räkna antal bett mot en spegel. Anxiolytiska effekter undersöktes vid koncentrationer på 0,1 µg/l, 15 µg/l och 1,5 µg/l. Effekter på ätbeteende undersöktes vid 0,15 µg/l och 1,5 µg/l. Eftersom serotonin är inblandat i embryonalutvecklingen testades de beteendemässiga effekterna av exponering för 1,5 µg/l under utvecklingen. Då citalopram sällan förekommer ensamt i miljön testades ett cocktailscenario där zebrafisk samtidigt exponerades för citalopram och den anxiogena substansen 17α-etinylestradiol (EE2).

Citalopram befanns ha anxiolytisk verkan på storspigg samt undertrycka ätbeteendet. Effekter på ätbeteendet uppstod inom en vecka efter exponering och vid den minsta testade dosen vilken var 0,15 µg/l. Storspigg som exponerats under embryonalutvecklingen var mer aggressiva, hade lägre lokomotoraktivitetoch gjorde fler utfall mot mat då de testades 100 dagar efter att exponeringen avslutats. Samtidigt exponering för citalopram och den anxiogena substansen 17α-etinylestradiol (EE2) gav tvetydiga resultat. Citalopram ensamt hade ingen signifikant påverkan på beteendet i detta försök. I skototaxitestet motverkade citalopram den anxiogena effekten av EE2 medan det förstärkte den anxiogena effekten i novel tank. Sammanfattningsvis har citalopram effekter på ekologiskt relevanta beteenden hos fisk i koncentrationer som förekommer i ytvatten. Det har också permanenta effekter på beteende om exponeringen sker under embryonalutvecklingen. Dessa resultat gör det sannolikt att citalopram och andra SSRI har ekologiska effekter i påverkade vattendrag.

Place, publisher, year, edition, pages
Huddinge: Södertörns högskola, 2017. 63 p.
Series
Södertörn Doctoral Dissertations, ISSN 1652-7399 ; 137
Keyword
Citalopram, SSRI, stickleback, Baltic, behaviour, fish, feeding, anxiety, boldness, serotonin, development, Storspigg, serotonin, östersjön, SSRI, läkemedel, miljö, citalopram, ätbeteende, beteende, utveckling
National Category
Environmental Sciences
Research subject
Environmental Studies; Baltic and East European studies
Identifiers
urn:nbn:se:sh:diva-32422 (URN)978-91-87843-96-9 (ISBN)978-91-87843-97-6 (ISBN)
Public defence
2017-06-01, MA624, Alfred Nobels allé 7, Huddinge, 13:00 (English)
Opponent
Supervisors
Funder
Stockholm County Council, 806/3.1.1/2014The Foundation for Baltic and East European Studies, 1352/3.1.1/2015
Available from: 2017-05-10 Created: 2017-04-19 Last updated: 2017-09-25Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMedScopus

Search in DiVA

By author/editor
Kellner, MartinPorseryd, TovePorsch-Hällström, IngerOlsén, K Håkan
By organisation
Environmental ScienceBiology
In the same journal
Aquatic Toxicology
Environmental SciencesBiological Sciences

Search outside of DiVA

GoogleGoogle Scholar

Altmetric score

Total: 259 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf