We studied the ecological consequences of widespread caffeine contamination by conducting an experiment focused on changes in the behavioral traits of wild perch (Perca fluviatilis) after waterborne exposure to 10 μg L-1 of caffeine. We monitored fish swimming performance during both light and dark conditions to study the effect of caffeine on fish activity and circadian rhythm, using a novel three-dimensional tracking system that enabled positioning even in complete darkness. All individuals underwent three behavioral trials-before exposure, after 24 h of exposure, and after 5 days of exposure. We did not observe any effect of the given caffeine concentration on fish activity under light or dark conditions. Regardless of caffeine exposure, fish swimming performance was significantly affected by both the light-dark conditions and repeating of behavioral trials. Individuals in both treatments swam significantly more during the light condition and their activity increased with time as follows: before exposure < after 24 h of exposure < after 5 days of exposure. We confirmed that the three-dimensional automated tracking system based on infrared sensors was highly effective for conducting behavioral experiments under completely dark conditions.

Department of Chemistry Umeå University SE 90187 Umeå Sweden

Department of Wildlife Fish and Environmental Studies Swedish University of Agricultural Sciences SE 90183 Umeå Sweden

Faculty of Fisheries and Protection of Waters South Bohemian Research Center of Aquaculture and Biodiversity of Hydrocenoses University of South Bohemia in Ceske Budejovice Zátiší 728 2 389 25 Vodňany Czech Republic

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Aguirre-Martínez GV, DelValls AT, Laura Martín-Díaz M. Yes, caffeine, ibuprofen, carbamazepine, novobiocin and tamoxifen have an effect on Corbicula fluminea (Müller, 1774) Ecotoxicology and Environmental Safety. 2015;120:142–154. doi: 10.1016/j.ecoenv.2015.05.036. PubMed DOI

Alderton W, Berghmans S, Butler P, Chassaing H, Fleming A, Golder Z, Richards F, Gardner I. Accumulation and metabolism of drugs and CYP probe substrates in zebrafish larvae. Xenobiotica. 2010;40:547–557. doi: 10.3109/00498254.2010.493960. PubMed DOI

aus der Beek T, Weber FA, Bergmann A, Hickmann S, Ebert I, Hein A, Küster A. Pharmaceuticals in the environment-Global occurrences and perspectives. Environmental Toxicology and Chemistry. 2016;35:823–835. doi: 10.1002/etc.3339. PubMed DOI

Azzouz A, Ballesteros E. Influence of seasonal climate differences on the pharmaceutical, hormone and personal care product removal efficiency of a drinking water treatment plant. Chemosphere. 2013;93:2046–2054. doi: 10.1016/j.chemosphere.2013.07.037. PubMed DOI

Baker DR, Kasprzyk-Hordern B. Spatial and temporal occurrence of pharmaceuticals and illicit drugs in the aqueous environment and during wastewater treatment: new developments. Science of the Total Environment. 2013;454-455:442–456. doi: 10.1016/j.scitotenv.2013.03.043. PubMed DOI

Barone JJ, Roberts HR. Caffeine consumption. Food and Chemical Toxicology. 1996;34:119–129. doi: 10.1016/0278-6915(95)00093-3. PubMed DOI

Biel-Maeso M, Baena-Nogueras RM, Corada-Fernández C, Lara-Martín PA. Occurrence, distribution and environmental risk of pharmaceutically active compounds (PhACs) in coastal and ocean waters from the Gulf of Cadiz (SW Spain) Science of the Total Environment. 2018;612:649–659. doi: 10.1016/j.scitotenv.2017.08.279. PubMed DOI

Boehmler W, Petko J, Woll M, Frey C, Thisse B, Thisse C, Canfield VA, Levenson R. Identification of zebrafish A2 adenosine receptors and expression in developing embryos. Gene Expr Patterns. 2009;9:144–151. doi: 10.1016/j.gep.2008.11.006. PubMed DOI PMC

Brodin T, Fick J, Jonsson M, Klaminder J. Dilute concentrations of a psychiatric drug alter behavior of fish from natural populations. Science. 2013;339:814–815. doi: 10.1126/science.1226850. PubMed DOI

Buerge IJ, Poiger T, Müller MD, Buser HR. Caffeine, an anthropogenic marker for wastewater contamination of surface waters. Environmental Science and Technology. 2003;37:691–700. doi: 10.1021/es020125z. PubMed DOI

Burkina V, Zlabek V, Zamaratskaia G. Effects of pharmaceuticals present in aquatic environment on Phase I metabolism in fish. Environmental Toxicology and Pharmacology. 2015;40:430–444. doi: 10.1016/j.etap.2015.07.016. PubMed DOI

Cantwell MG, Katz DR, Sullivan JC, Borci T, Chen RF. Caffeine in Boston Harbor past and present, assessing its utility as a tracer of wastewater contamination in an urban estuary. Marine Pollution Bulletin. 2016;108:321–324. doi: 10.1016/j.marpolbul.2016.04.006. PubMed DOI

Cerveny D, Brodin T, Cisar P, McCallum ES, Fick J (2020) Bioconcentration and behavioral effects of four benzodiazepines and their environmentally relevant mixture in wild fish. Science of the Total Environment 702. 10.1016/j.scitotenv.2019.134780 PubMed

Charuaud L, Jarde E, Jaffrezic A, Thomas MF, Le Bot B. Veterinary pharmaceutical residues from natural water to tap water: sales, occurrence and fate. Journal of Hazardous Materials. 2019;361:169–186. doi: 10.1016/j.jhazmat.2018.08.075. PubMed DOI

Comeau F, Surette C, Brun GL, Losier R. The occurrence of acidic drugs and caffeine in sewage effluents and receiving waters from three coastal watersheds in Atlantic Canada. Science of the Total Environment. 2008;396:132–146. doi: 10.1016/j.scitotenv.2008.02.031. PubMed DOI

Cui Y, Wang Y, Pan C, Li R, Xue R, Guo J, Zhang R. Spatiotemporal distributions, source apportionment and potential risks of 15 pharmaceuticals and personal care products (PPCPs) in Qinzhou Bay, South China. Marine Pollution Bulletin. 2019;141:104–111. doi: 10.1016/j.marpolbul.2019.02.012. PubMed DOI

Du SNN, McCallum ES, Vaseghi-Shanjani M, Choi JA, Warriner TR, Balshine S, Scott GR. Metabolic costs of exposure to wastewater effluent lead to compensatory adjustments in respiratory physiology in bluegill sunfish. Environmental Science and Technology. 2018;52:801–811. doi: 10.1021/acs.est.7b03745. PubMed DOI

Einöther SJL, Giesbrecht T. Caffeine as an attention enhancer: Reviewing existing assumptions. Psychopharmacology. 2013;225:251–274. doi: 10.1007/s00213-012-2917-4. PubMed DOI

Faillace MP, Pisera-Fuster A, Bernabeu R. Evaluation of the rewarding properties of nicotine and caffeine by implementation of a five-choice conditioned place preference task in zebrafish. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2018;84:160–172. doi: 10.1016/j.pnpbp.2018.02.001. PubMed DOI

Ferreira AP, De Lourdes C, Da Cunha N. Anthropic pollution in aquatic environment: development of a caffeine indicator. International Journal of Environmental Health Research. 2005;15:303–311. doi: 10.1080/09603120500155898. PubMed DOI

Fick J, Brodin T, Heynen M, Klaminder J, Jonsson M, Grabicova K, Randak T, Grabic R, Kodes V, Slobodnik J, Sweetman A, Earnshaw M, Caracciolo AB, Lettieri T, Loos R. Screening of benzodiazepines in thirty European rivers. Chemosphere. 2017;176:324–332. doi: 10.1016/j.chemosphere.2017.02.126. PubMed DOI

Hölker F, Dörner H, Schulze T, Haertel-Borer SS, Peacor SD, Mehner T. Species-specific responses of planktivorous fish to the introduction of a new piscivore: implications for prey fitness. Freshwater Biology. 2007;52:1793–1806. doi: 10.1111/j.1365-2427.2007.01810.x. DOI

Ide AH, Osawa RA, Marcante LO, da Costa PJ, de Azevedo JCR (2017) Occurrence of pharmaceutical products, female sex hormones and caffeine in a subtropical region in Brazil. Clean - Soil, Air, Water 45. 10.1002/clen.201700334

Kasprzyk-Hordern B, Dinsdale RM, Guwy AJ. The occurrence of pharmaceuticals, personal care products, endocrine disruptors and illicit drugs in surface water in South Wales, UK. Water Research. 2008;42:3498–3518. doi: 10.1016/j.watres.2008.04.026. PubMed DOI

Kellner M, Porseryd T, Hallgren S, Porsch-Hällström I, Hansen SH, Olsén KH. Waterborne citalopram has anxiolytic effects and increases locomotor activity in the three-spine stickleback (Gasterosteus aculeatus) Aquatic Toxicology. 2016;173:19–28. doi: 10.1016/j.aquatox.2015.12.026. PubMed DOI

Khan GA, Lindberg R, Grabic R, Fick J. The development and application of a system for simultaneously determining anti-infectives and nasal decongestants using on-line solid-phase extraction and liquid chromatography-tandem mass spectrometry. Journal of Pharmaceutical and Biomedical Analysis. 2012;66:24–32. doi: 10.1016/j.jpba.2012.02.011. PubMed DOI

Ladu F, Mwaffo V, Li J, Macrì S, Porfiri M. Acute caffeine administration affects zebrafish response to a robotic stimulus. Behavioural Brain Research. 2015;289:48–54. doi: 10.1016/j.bbr.2015.04.020. PubMed DOI

Lam MW, Young CJ, Brain RA, Johnson DJ, Hanson ML, Wilson CJ, Richards SM, Solomon KR, Mabury SA. Aquatic persistence of eight pharmaceuticals in a microcosm study. Environmental Toxicology and Chemistry. 2004;23:1431–1440. doi: 10.1897/03-421. PubMed DOI

Lindberg RH, Ostman M, Olofsson U, Grabic R, Fick J. Occurrence and behaviour of 105 active pharmaceutical ingredients in sewage waters of a municipal sewer collection system. Water Research. 2014;58:221–229. doi: 10.1016/j.watres.2014.03.076. PubMed DOI

Marin MF, Lord C, Andrews J, Juster RP, Sindi S, Arsenault-Lapierre G, Fiocco AJ, Lupien SJ. Chronic stress, cognitive functioning and mental health. Neurobiology of Learning and Memory. 2011;96:583–595. doi: 10.1016/j.nlm.2011.02.016. PubMed DOI

McCallum ES, Bose APH, Warriner TR, Balshine S. An evaluation of behavioural endpoints: the pharmaceutical pollutant fluoxetine decreases aggression across multiple contexts in round goby (Neogobius melanostomus) Chemosphere. 2017;175:401–410. doi: 10.1016/j.chemosphere.2017.02.059. PubMed DOI

Meffe R, de Bustamante I. Emerging organic contaminants in surface water and groundwater: a first overview of the situation in Italy. Science of the Total Environment. 2014;481:280–295. doi: 10.1016/j.scitotenv.2014.02.053. PubMed DOI

Metcalfe CD, Miao XS, Koenig BG, Struger J. Distribution of acidic and neutral drugs in surface waters near sewage treatment plants in the lower Great Lakes, Canada. Environmental Toxicology and Chemistry. 2003;22:2881–2889. doi: 10.1897/02-627. PubMed DOI

Moore MT, Greenway SL, Farris JL, Guerra B. Assessing caffeine as an emerging environmental concern using conventional approaches. Archives of Environmental Contamination and Toxicology. 2008;54:31–35. doi: 10.1007/s00244-007-9059-4. PubMed DOI

Neri D, Ruberto T, Mwaffo V, Bartolini T, Porfiri M. Social environment modulates anxiogenic effects of caffeine in zebrafish. Behavioural Pharmacology. 2019;30:45–58. doi: 10.1097/fbp.0000000000000415. PubMed DOI

Niemuth NJ, Jordan R, Crago J, Blanksma C, Johnson R, Klaper RD. Metformin exposure at environmentally relevant concentrations causes potential endocrine disruption in adult male fish. Environmental Toxicology and Chemistry. 2015;34:291–296. doi: 10.1002/etc.2793. PubMed DOI PMC

Pando MP, Sassone-Corsi P. Unraveling the mechanisms of the vertebrate circadian clock: zebrafish may light the way. BioEssays. 2002;24:419–426. doi: 10.1002/bies.10091. PubMed DOI

Patiño MAL, Rodríguez-Illamola A, Conde-Sieira M, Soengas JL, Míguez JM. Daily rhythmic expression patterns of clock1a, bmal1, and per1 genes in retina and hypothalamus of the rainbow trout, Oncorhynchus mykiss. Chronobiology International. 2011;28:381–389. doi: 10.3109/07420528.2011.566398. PubMed DOI

Pires A, Almeida Â, Calisto V, Schneider RJ, Esteves VI, Wrona FJ, Soares AMVM, Figueira E, Freitas R. Long-term exposure of polychaetes to caffeine: biochemical alterations induced in Diopatra neapolitana and Arenicola marina. Environmental Pollution. 2016;214:456–463. doi: 10.1016/j.envpol.2016.04.031. PubMed DOI

Reyes CM, Cornelis MC (2018) Caffeine in the diet: country-level consumption and guidelines. Nutrients 10. 10.3390/nu10111772 PubMed PMC

Rodríguez-Gil JL, Cáceres N, Dafouz R, Valcárcel Y. Caffeine and paraxanthine in aquatic systems: global exposure distributions and probabilistic risk assessment. Science of the Total Environment. 2018;612:1058–1071. doi: 10.1016/j.scitotenv.2017.08.066. PubMed DOI

Ruiz-Oliveira J, Silva PF, Luchiari AC (2019) Coffee time: low caffeine dose promotes attention and focus in zebrafish. Learning and Behavior. 10.3758/s13420-018-0369-3 PubMed

Saad M, Verbueken E, Pype C, Casteleyn C, Van Ginneken C, Maes L, Cos P, Van Cruchten S. In vitro CYP1A activity in the zebrafish: temporal but low metabolite levels during organogenesis and lack of gender differences in the adult stage. Reproductive Toxicology. 2016;64:50–56. doi: 10.1016/j.reprotox.2016.03.049. PubMed DOI

Saberioon MM, Cisar P. Automated multiple fish tracking in three-dimension using a structured light sensor. Computers and Electronics in Agriculture. 2016;121:215–221. doi: 10.1016/j.compag.2015.12.014. DOI

Sánchez-Vázquez FJ, López-Olmeda JF, Vera LM, Migaud H, López-Patiño MA, Míguez JM (2019) Environmental cycles, melatonin, and circadian control of stress response in fish. Frontiers in Endocrinology 10. 10.3389/fendo.2019.00279 PubMed PMC

Spongberg AL, Witter JD, Acuña J, Vargas J, Murillo M, Umaña G, Gómez E, Perez G. Reconnaissance of selected PPCP compounds in Costa Rican surface waters. Water Research. 2011;45:6709–6717. doi: 10.1016/j.watres.2011.10.004. PubMed DOI

Steele WB, Mole RA, Brooks BW (2018) Experimental protocol for examining behavioral response profiles in larval fish: application to the neuro-stimulant caffeine. Journal of Visualized Experiments 2018. 10.3791/57938 PubMed PMC

Sui Q, Cao X, Lu S, Zhao W, Qiu Z, Yu G. Occurrence, sources and fate of pharmaceuticals and personal care products in the groundwater: a review. Emerging Contaminants. 2015;1:14–24. doi: 10.1016/j.emcon.2015.07.001. DOI

Tamai TK, Young LC, Cox CA, Whitmore D. Light acts on the zebrafish circadian clock to suppress rhythmic mitosis and cell proliferation. Journal of Biological Rhythms. 2012;27:226–236. doi: 10.1177/0748730412440861. PubMed DOI

Yang Y, Ok YS, Kim K-H, Kwon EE, Tsang YF. Occurrences and removal of pharmaceuticals and personal care products (PPCPs) in drinking water and water/sewage treatment plants: a review. Science of the Total Environment. 2017;596-597:303–320. doi: 10.1016/j.scitotenv.2017.04.102. PubMed DOI

Zamora L, Moreno-Amich R. Quantifying the activity and movement of perch in a temperate lake by integrating acoustic telemetry and a geographic information system. Hydrobiologia. 2002;483:209–218. doi: 10.1023/a:1021396016424. DOI

Zhang Q, Cheng J, Xin Q. Effects of tetracycline on developmental toxicity and molecular responses in zebrafish (Danio rerio) embryos. Ecotoxicology. 2015;24:707–719. doi: 10.1007/s10646-015-1417-9. PubMed DOI

Zhou H, Wu C, Huang X, Gao M, Wen X, Tsuno H, Tanaka H. Occurrence of selected pharmaceuticals and caffeine in sewage treatment plants and receiving rivers in Beijing, China. Water Environment Research. 2010;82:2239–2248. doi: 10.2175/106143010x12681059116653. PubMed DOI

Zhou S, Chen Q, Di Paolo C, Shao Y, Hollert H, Seiler T-B. Behavioral profile alterations in zebrafish larvae exposed to environmentally relevant concentrations of eight priority pharmaceuticals. Sci Total Environ. 2019;664:89–98. doi: 10.1016/j.scitotenv.2019.01.300. PubMed DOI

Zhou SB, Di Paolo C, Wu X, Shao Y, Seiler TB, Hollert H. Optimization of screening-level risk assessment and priority selection of emerging pollutants - the case of pharmaceuticals in European surface waters. Environment International. 2019;128:1–10. doi: 10.1016/j.envint.2019.04.034. PubMed DOI

Insights into environmental caffeine contamination in ecotoxicological biomarkers and potential health effects of Danio rerio