Persistent and transgenerational effects of risperidone in zebrafish
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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.
KeywordsDanio rerio Persistent effects Transgenerational toxicology Prey-predator relationship Behavior
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).
The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
- 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
- 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
- Bhandari RK, Tillitt DE (2015) Transgenerational effects from early developmental exposures to bisphenol A. 1–5. https://doi.org/10.1038/srep09303
- Blaser R, Gerlai R (2006) Behavioral phenotyping in zebrafish: comparison of three behavioral quantification methods. Behav Brain Res 38:456–469Google Scholar
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- Westerfield M (2000) The zebrafish book. A guide for the laboratory use of zebrafish (Danio rerio), 4th Edition. University of Oregon Press, EugeneGoogle Scholar
- 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