Advertisement

Persistent and transgenerational effects of risperidone in zebrafish

  • Fabiana Kalichak
  • Heloisa Helena de Alcantara Barcellos
  • Renan Idalencio
  • Gessi Koakoski
  • Suelen Mendonça Soares
  • Aline Pompermaier
  • Mainara Rossini
  • Leonardo José Gil BarcellosEmail author
Research Article
  • 21 Downloads

Abstract

Since behavior is the connection between the internal physiological processes of an animal and its interaction with the environment, a complete behavioral repertoire is crucial for fish survival and fitness, at both the individual and population levels. Thus, unintended exposure of non-target organisms to antipsychotic residues in the environment can impact their normal behavior, and some of these behavioral changes can be seen during the entire life of the animal and passed to subsequent generations. Although there are some reports related to transgenerational toxicology, little is known of the long-term consequences of exposure to pharmaceutical compounds such as risperidone. Here, we show that zebrafish exposed to risperidone (RISP) during embryonic and larval stages presented impaired anti-predatory behavior during adulthood, characterizing a persistent effect. We also show that some of these behavioral changes are present in the following generation, characterizing a transgenerational effect. This suggests that even short exposures to environmentally relevant concentrations, at essential stages of development, can persist throughout the whole life of the zebrafish, including its offspring. From an environmental perspective, our results suggested possible risks and long-term consequences associated with drug residues in water, which can affect aquatic life and endanger species that depend on appropriate behavioral responses for survival.

Keywords

Danio rerio Persistent effects Transgenerational toxicology Prey-predator relationship Behavior 

Notes

Funding information

This study was funded by a CNPq research fellowship (303263/2018-0) to Leonardo G. Barcellos.

Compliance with ethical standards

This study was approved by the Animal Use Ethics Committee (CEUA) of the University of Passo Fundo, UPF, Passo Fundo, RS, Brazil (Protocol 009.2015 – CEUA) and complied with the guidelines of the National Council for the Control of Animal Experimentation (CONCEA).

Disclaimer

The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Supplementary material

11356_2019_5890_MOESM1_ESM.docx (173 kb)
ESM 1 (DOCX 173 kb)

References

  1. Abreu MS, Giacomini ACV, Koakoski G, Oliveira TA, Gusso D, Baldisserotto B, Barcellos LJG (2015) Effects of waterborne fluoxetine on stress response and osmoregulation in zebrafish. Environ Toxicol Pharmacol 40:704–707.  https://doi.org/10.1016/j.etap.2015.09.001 CrossRefGoogle Scholar
  2. Avdesh A, Chen M, Martin-iverson MT, et al (2012) Regular care and maintenance of a zebrafish (Danio rerio) laboratory: an introduction.  https://doi.org/10.3791/4196
  3. Baker DR, Barron L, Kasprzyk-hordern B (2014) Illicit and pharmaceutical drug consumption estimated via wastewater analysis. Part A: chemical analysis and drug use estimates. Sci Total Environ 487:629–641.  https://doi.org/10.1016/j.scitotenv.2013.11.107 CrossRefGoogle Scholar
  4. Bardgett ME, Franks-henry JM, Colemire KR et al (2013) Adult rats treated with risperidone during development are hyperactive. Exp Clin Psychopharmacol 21:259–267.  https://doi.org/10.1037/a0031972 AdultCrossRefGoogle Scholar
  5. Barreto RE (2016) Mianserin affects alarm reaction to conspecific chemical alarm cues in Nile tilapia. Fish Physiol Biochem 43:193–201.  https://doi.org/10.1007/s10695-016-0279-2 CrossRefGoogle Scholar
  6. Bell RD, Rypstra AL, Persons MH (2006) The effect of predator hunger on chemically mediated antipredator responses and survival in the wolf spider Pardosa milvina (Araneae: Lycosidae).  https://doi.org/10.1111/j.1439-0310.2006.01244.x
  7. Bhandari RK, Tillitt DE (2015) Transgenerational effects from early developmental exposures to bisphenol A. 1–5.  https://doi.org/10.1038/srep09303
  8. Blaser R, Gerlai R (2006) Behavioral phenotyping in zebrafish: comparison of three behavioral quantification methods. Behav Brain Res 38:456–469Google Scholar
  9. Bruce G, Pleus R, Snyder S (2010) Toxicological relevance of pharmaceuticals in drinking water. Environ Sci Technol 44:5619–5626CrossRefGoogle Scholar
  10. Bruner-Tran K, Osteen K (2011) Developmental exposure to TCDD reduces fertility and negatively affects pregnancy outcomes across multiple generations. Reprod Toxicol 31:344–350.  https://doi.org/10.1016/j.reprotox.2010.10.003 CrossRefGoogle Scholar
  11. Chakravarthy S, Sadagopan S, Nair A, Sukumaran SK (2014) Zebrafish as an in vivo high-throughput. 11:154–166. doi:  https://doi.org/10.1089/zeb.2013.0924
  12. Clift D, Richendrfer H, Thorn RJ, et al (2014) High-throughput analysis of behavior in zebrafish larvae: 11:455–461. doi:  https://doi.org/10.1089/zeb.2014.0989
  13. Colwill RM, Creton R (2011) Locomotor behaviors in zebrafish (Danio rerio) larvae. Behav Process 86:222–229.  https://doi.org/10.1016/j.beproc.2010.12.003 CrossRefGoogle Scholar
  14. Endres H, Rosa J, Kabaselle C et al (2017) Neuroscience letters first evidence that waterborne methylphenidate alters endocrine and behavioral stress responses in zebrafish. Neurosci Lett 650:114–117.  https://doi.org/10.1016/j.neulet.2017.04.039 CrossRefGoogle Scholar
  15. Engeszer RE, Ryan MJ, Parichy DM (2004) Learned social preference in zebrafish. Curr Biol 14:881–884.  https://doi.org/10.1016/j.cub.2004.04.042 CrossRefGoogle Scholar
  16. Fabbri E (2015) Pharmaceuticals in the environment: expected and unexpected effects on aquatic. fauna. 1340:20–28.  https://doi.org/10.1111/nyas.12605 Google Scholar
  17. Fraysse B, Mons R, Garric J (2006) Development of a zebrafish 4-day embryo-larval bioassay to assess toxicity of chemicals. Ecotoxicol Environ Saf 63:253–267.  https://doi.org/10.1016/j.ecoenv.2004.10.015 CrossRefGoogle Scholar
  18. Galus M, Jeyaranjaan J, Smith E, Li H, Metcalfe C, Wilson JY (2013) Chronic effects of exposure to a pharmaceutical mixture and municipal wastewater in zebrafish. Aquat Toxicol 132–133:212–222.  https://doi.org/10.1016/j.aquatox.2012.12.016 CrossRefGoogle Scholar
  19. Gao D, Lin J, Ou K, Chen Y, Li H, Dai Q, Yu Z, Zuo Z, Wang C (2018) Embryonic exposure to benzo (a) pyrene inhibits reproductive capability in adult female zebra fish and correlation with DNA. Environ Pollut 240:403–411.  https://doi.org/10.1016/j.envpol.2018.04.139 CrossRefGoogle Scholar
  20. Giacomini ACVV, Abreu MS, Giacomini LV, Siebel AM, Zimerman FF, Rambo CL, Mocelin R, Bonan CD, Piato AL, Barcellos LJG, (2016) Fluoxetine and diazepam acutely modulate stress induced-behavior. Behavioural Brain Research 296:301-310CrossRefGoogle Scholar
  21. Herbert-Read J, Rosen E, Szorkovszky A et al (2018) How predation shapes the social interaction rules of shoaling fish. Proc R Soc B 284:20171126CrossRefGoogle Scholar
  22. Horacek J, Bubenikova-valesova V, Kopecek M, et al (2006) Mechanism of action of atypical antipsychotic drugs and the neurobiology of schizophrenia. 20:389–409Google Scholar
  23. Idalencio R, Kalichak F, Rosa JGS, Oliveira TA, Koakoski G, Gusso D, Abreu MS, Giacomini ACV, Barcellos HHA, Piato AL, Barcellos LJG (2015) Waterborne risperidone decreases stress response in zebrafish. PLoS One 10:e0140800.  https://doi.org/10.1371/journal.pone.0140800 CrossRefGoogle Scholar
  24. Igartúa DE, Calienni MN, Feas DA, Chiaramoni NS, del Valle Alonso S, Prieto MJ (2015) Development of nutraceutical emulsions as risperidone delivery systems: characterization and toxicological studies. J Parm Sci 104:4142–4152.  https://doi.org/10.1002/jps.24636 CrossRefGoogle Scholar
  25. Irons TD, Macphail RC, Hunter DL, Padilla S (2010) Neurotoxicology and teratology acute neuroactive drug exposures alter locomotor activity in larval zebra fi sh. Neurotoxicol Teratol 32:84–90.  https://doi.org/10.1016/j.ntt.2009.04.066 CrossRefGoogle Scholar
  26. K’Oreje K, Vergeynst L, Ombaka D et al (2016) Occurrence patterns of pharmaceutical residues in wastewater, surface water and groundwater of Nairobi and Kisumu city, Kenya. Chemosphere 149:238–244.  https://doi.org/10.1016/j.chemosphere.2016.01.095 CrossRefGoogle Scholar
  27. Kalichak F, Idalencio R, Rosa JGS, Oliveira TA, Koakoski G, Gusso D, Abreu MS, Giacomini ACV, Barcellos HHA, Fagundes M, Piato AL, Barcellos LJG (2016) Waterborne psychoactive drugs impair the initial development of zebrafish. Environ Toxicol Pharmacol 41:89–94.  https://doi.org/10.1016/j.etap.2015.11.014 CrossRefGoogle Scholar
  28. Kalichak F, Idalencio R, Da Rosa JGS et al (2017) Psychotropic in the environment: risperidone residues affect the behavior of fish larvae. Sci Rep 7.  https://doi.org/10.1038/s41598-017-14575-7
  29. Kelley JL, Magurran A (2003) Learned predator recognition and antipredator responses in fishes. Fish Fish 4:216–226CrossRefGoogle Scholar
  30. Kimmel CB, Ballard WW, Kimmel SR et al (1995) Stages of embryonic development of the zebrafish. Dev Dyn 203(3):253–310CrossRefGoogle Scholar
  31. Kirsten K, Fior D, Kreutz LC, Barcellos LJG (2018) First description of behavior and immune system relationship in fish. Sci Rep 8:846.  https://doi.org/10.1038/s41598-018-19276-3 CrossRefGoogle Scholar
  32. Koakoski G, Quevedo RM, Ferreira D, Oliveira TA, da Rosa JGS, de Abreu MS, Gusso D, Marqueze A, Kreutz LC, Giacomini ACV, Fagundes M, Barcellos LJG (2014) Agrichemicals chronically inhibit the cortisol response to stress in fish. Chemosphere 112:85–91.  https://doi.org/10.1016/j.chemosphere.2014.02.083 CrossRefGoogle Scholar
  33. Kysil EV, Meshalkina DA, Frick EE, Echevarria DJ, Rosemberg DB, Maximino C, Lima MG, Abreu MS, Giacomini AC, Barcellos LJG, Song C, Kalueff AV (2017) Comparative analyses of zebrafish anxiety-like behavior using conflict-based novelty tests. Zebrafish 14:197–208.  https://doi.org/10.1089/zeb.2016.1415 CrossRefGoogle Scholar
  34. Lorenzi V, Choe R, Schlenk D (2014) Effects of environmental exposure to diazepam on the reproductive behavior of fathead minnow, Pimephales promelas. 1–8.  https://doi.org/10.1002/tox
  35. Manikkam M, Tracey R, Guerrero-bosagna C, Skinner MK (2012) Dioxin (TCDD) induces epigenetic transgenerational inheritance of adult onset disease and sperm epimutations. PLoS One 7:e46249.  https://doi.org/10.1371/journal.pone.0046249 CrossRefGoogle Scholar
  36. Mannens G, Meuldermans W, Snoeck E, Heycants J (1994) Plasma protein binding of risperidone and its distribution in blood. Psychopharmacology 114:566–572CrossRefGoogle Scholar
  37. Mansur RB, Brietzke E, McIntyre RS (2015) Is there a “metabolic-mood syndrome”? A review of the relationship between obesity and mood disorders. Neurosci Biobehav Rev 52:89–104.  https://doi.org/10.1016/j.neubiorev.2014.12.017 CrossRefGoogle Scholar
  38. Marcon M, Herrmann AP, Mocelin R, Rambo CL, Koakoski G, Abreu MS, Conterato GMM, Kist LW, Bogo MR, Zanatta L, Barcellos LJG, Piato AL (2016) Prevention of unpredictable chronic stress-related phenomena in zebrafish exposed to bromazepam, fluoxetine and nortriptyline. Psychopharmacology 233:3815–3824.  https://doi.org/10.1007/s00213-016-4408-5 CrossRefGoogle Scholar
  39. Martinez-Sales M, Garcia-Ximenz F, Espinós F (2015) Zebrafish as a possible bioindicator of organic pollutants with effects on reproduction in drinking waters. J Environ Sci 33:254–260.  https://doi.org/10.1016/j.jes.2014.11.012 CrossRefGoogle Scholar
  40. Mccarthy DM, Morgan TJ, Lowe SE et al (2018) Nicotine exposure of male mice produces behavioral impairment in multiple generations of descendants. PLoS Biol 16(10):e2006497.  https://doi.org/10.1371/journal.pbio.2006497
  41. McLean DL, Fetcho JR (2004) Relationship of tyrosine hydroxylase and serotonin immunoreactivity to sensorimotor circuitry in larval zebrafish. J Comp Neurol 71:57–71.  https://doi.org/10.1002/cne.20281 CrossRefGoogle Scholar
  42. Minguez L, Rakotomalala C, Kientz-bouchart V (2015) Transgenerational effects of two antidepressants (sertraline and venlafaxine) on Daphnia magna life history traits. Environ Sci Technol 49:1148–1155.  https://doi.org/10.1021/es504808g CrossRefGoogle Scholar
  43. Mondin E, Luis R, Pobbe H, Jr HZ (2015) Physiology & behavior behavioral consequences of predator stress in the rat elevated T-maze. Physiol Behav 146:28–35.  https://doi.org/10.1016/j.physbeh.2015.04.019 CrossRefGoogle Scholar
  44. Ojha S, Fainberg HP, Sebert S, Budge H, Symonds ME (2015) Maternal health and eating habits: metabolic consequences and impact on child health. Trends Mol Med 21:126–133.  https://doi.org/10.1016/j.molmed.2014.12.005 CrossRefGoogle Scholar
  45. Orger MB, De Polavieja GG (2017) Zebrafish behavior: opportunities and challenges. Annu Rev Neurosci 40:125–147CrossRefGoogle Scholar
  46. Osuna-luque J, Rodríguez-ramos Á, Ruiz-rubio M et al (2018) Behavioral mechanisms that depend on dopamine and serotonin in Caenorhabditis elegans interact with the antipsychotics risperidone and aripiprazole. J Exp Neurosci 12:1–11.  https://doi.org/10.1177/1179069518798628 CrossRefGoogle Scholar
  47. Painter M, Buerkley M, Julius M et al (2009) Antidepressants at environmentally relevant concentrations affect predator avoidance behavior of larval fathead minnows (Pimephales promelas). Environ Toxicol Chem 28:2677–2684CrossRefGoogle Scholar
  48. Pomati F, Castiglione S, Zuccato E et al (2006) Effects of a complex mixture of therapeutic drugs at environmental levels on human embryonic cells. Environ Sci Technol 40:2442–2447CrossRefGoogle Scholar
  49. Prieto MJ, Gutierrez HC, Arévalo RA et al (2012) Effect of risperidone and fluoxetine on the movement and neurochemical changes of zebrafish. Open J Med Chem 2012:129–138CrossRefGoogle Scholar
  50. Santangeli S, Maradonna F, Gioacchi G et al (2016) BPA-induced deregulation of epigenetic patterns: effects on female zebrafish reproduction. Sci Rep 6.  https://doi.org/10.1038/srep21982
  51. Serra EL, Medalha CC, Mattioli R (1999) Natural preference of zebrafish (Danio rerio) for a dark environment. Braz J Med Biol Res 32:1551–1553CrossRefGoogle Scholar
  52. Shi Y, Li M, Song C, Xu Q, Huo R, Shen L, Xing Q, Cui D, Li W, Zhao J, He L, Qin S (2017) Combined study of genetic and epigenetic biomarker risperidone treatment efficacy in Chinese Han schizophrenia patients. Transl Psychiatry 7:e1170.  https://doi.org/10.1038/tp.2017.143 CrossRefGoogle Scholar
  53. Singh KP, Singh MK (2017) Progress in neuro-psychopharmacology & biological psychiatry in utero exposure to atypical antipsychotic drug, risperidone: effects on fetal neurotoxicity in hippocampal region and cognitive impairment in rat offspring. PNP 75:35–44.  https://doi.org/10.1016/j.pnpbp.2016.12.006 Google Scholar
  54. Snyder SA (2008) Occurrence, Treatment, and Toxicological Relevance of EDCs and Pharmaceuticals in Water. Ozone Sci Eng 30:6569.  https://doi.org/10.1080/01919510701799278 CrossRefGoogle Scholar
  55. Stewart WJ, Cardenas GS, Mchenry MJ (2013) Zebrafish larvae evade predators by sensing water flow. J Exp Biol 2016:388–398.  https://doi.org/10.1242/jeb.072751 CrossRefGoogle Scholar
  56. Tang W, Ho S (2007) Epigenetic reprogramming and imprinting in origins of disease. Rev Endocr Metab Disord 8:173–182.  https://doi.org/10.1007/s11154-007-9042-4 CrossRefGoogle Scholar
  57. Tang Z, Huang Q, Wu H et al (2017) The behavioral response of prey fish to predators: the role of predator size. PeerJ.  https://doi.org/10.7717/peerj.3222
  58. Vasilieva N, Cherapanova E, von Holst D, Apfelbach R (2000) Predator odour and its impact on male fertility and reproduction in Phodopus campbelli hamsters. Naturwissenschaften 87:312–314CrossRefGoogle Scholar
  59. Veldhoen N, Skirrow RC, Brown LLY et al (2014) Effects of acute exposure to the non-steroidal anti-inflammatory drug ibuprofen on the developing North American bullfrog (Rana catesbeiana) tadpole. Environ Sci Technol.  https://doi.org/10.1021/es502539g
  60. Vidal-Dorsch D, Bay S, Maruya K et al (2012) Contaminants of emerging concern in municipal wastewater effluents and marine receiving water. Environ Toxicol Chem 31:2674–2682.  https://doi.org/10.1002/etc.2004 CrossRefGoogle Scholar
  61. Weinberger J II, Klaper R (2014) Environmental concentrations of the selective serotonin reuptake inhibitor fluoxetine impact specific behaviors involved in reproduction, feeding and predator avoidance in the fish Pimephales promelas (fathead minnow). Aquat Toxicol 151:77–83.  https://doi.org/10.1016/j.aquatox.2013.10.012 EnvironmentalCrossRefGoogle Scholar
  62. Westerfield M (2000) The zebrafish book. A guide for the laboratory use of zebrafish (Danio rerio), 4th Edition. University of Oregon Press, EugeneGoogle Scholar
  63. Wilson KS, Tucker CS, Holmes MC et al (2016) Early-life glucocorticoids programme behaviour and metabolism in adulthood in zebrafish. J Endocrinol.  https://doi.org/10.1530/JOE-15-0376
  64. Zuo J, Liu Z, Ouyang X, Liu H (2008) Distinct neurobehavioral consequences of prenatal exposure to sulpiride (SUL) and risperidone (RIS) in rats. Prog Neuropsychopharmacology Biol Psychiatry 32(32):387–397.  https://doi.org/10.1016/j.pnpbp.2007.09.005 CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Fabiana Kalichak
    • 1
    • 2
  • Heloisa Helena de Alcantara Barcellos
    • 1
    • 3
  • Renan Idalencio
    • 1
    • 3
  • Gessi Koakoski
    • 4
  • Suelen Mendonça Soares
    • 1
  • Aline Pompermaier
    • 5
  • Mainara Rossini
    • 3
  • Leonardo José Gil Barcellos
    • 1
    • 3
    • 4
    • 5
    Email author
  1. 1.Programa de Pós-Graduação em FarmacologiaUniversidade Federal de Santa Maria (UFSM)Santa MariaBrazil
  2. 2.Curso de Medicina VeterináriaFaculdades Integradas do Vale do Iguaçu (Uniguaçu)União da VitóriaBrazil
  3. 3.Curso de Medicina VeterináriaUniversidade de Passo Fundo (UPF)Passo FundoBrazil
  4. 4.Programa de Pós-Graduação em BioexperimentaçãoUniversidade de Passo Fundo (UPF)Passo FundoBrazil
  5. 5.Programa de Pós-Graduação em Ciências AmbientaisUniversidade de Passo Fundo (UPF)Passo FundoBrazil

Personalised recommendations