Skip to main content

Advertisement

SpringerLink
Log in

Characterization of neurotransmitter profiles in Daphnia magna juveniles exposed to environmental concentrations of antidepressants and anxiolytic and antihypertensive drugs using liquid chromatography–tandem mass spectrometry

  • Research Paper
  • Published:
Analytical and Bioanalytical Chemistry Aims and scope Submit manuscript

Abstract

It has been reported that antidepressant, anxiolytic and antihypertensive drugs alter the behavior and reproduction of the microcrustacean Daphnia magna at very low concentrations. However, there is little evidence for how these drugs act on their neurotransmitter targets. A method based on hydrophilic interaction liquid chromatography coupled with tandem mass spectrometry has been developed and applied for the first time using D. magna extracts and validated by studying the changes in the levels of a suite of neurotransmitters caused by five different neuroactive pharmaceuticals (fluoxetine, venlafaxine, carbamazepine, propranolol, and diazepam) dosed at 100 ng/L. Sample extraction and chromatographic and detection conditions were optimized for accurate detection of the selected neurotransmitters in whole D. magna organisms. The method allowed the simultaneous quantification of eight neurotransmitters belonging to six neuroendocrine systems: the dopaminergic, adrenergic, GABAergic, serotoninergic, histaminergic, and cholinergic systems. Neurotransmitters were eluted with a ZIC-HILIC column and quantified by tandem mass spectrometry in positive electrospray ionization mode performed in multiple reaction monitoring mode. All method validation assays (i.e., quality controls for linearity, sensitivity, accuracy, precision, stability, recovery, matrix effect, and carryover) were compliant with the standard requirements for similar analysis. Exposure to fluoxetine enhanced serotonin concentrations, whereas exposure to diazepam decreased the levels of dopamine, and exposure to propranolol increased the levels of norepinephrine. Exposure to both propranolol and diazepam decreased the levels of histamine. The results show the usefulness of this approach for environmental neurotoxicity studies.

Graphical abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Kurian MA, Gissen P, Smith M, Heales SJR, Clayton PT. The monoamine neurotransmitter disorders: an expanding range of neurological syndromes. Lancet Neurol. 2011;(8):721–33. https://doi.org/10.1016/S1474-4422(11)70141-7.

  2. Waye A, Trudeau VL. Neuroendocrine disruption: more than hormones are upset. J Toxicol Environ Health B Crit Rev. 2011;14(5–7):270–91. https://doi.org/10.1080/10937404.2011.578273.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Scott GR, Sloman KA. The effects of environmental pollutants on complex fish behaviour: integrating behavioural and physiological indicators of toxicity. Aquat Toxicol. 2004;68(4):369–92. https://doi.org/10.1016/j.aquatox.2004.03.016.

    Article  CAS  PubMed  Google Scholar 

  4. Tufi S, Leonards P, Lamoree M, De Boer J, Legler J, Legradi J. Changes in neurotransmitter profiles during early zebrafish (Danio rerio) development and after pesticide exposure. Environ Sci Technol. 2016;50(6):3222–30. https://doi.org/10.1021/acs.est.5b05665.

    Article  CAS  PubMed  Google Scholar 

  5. Kaplan S. Review: pharmacological pollution in water. Crit Rev Environ Sci Technol. 2013;43(10):1074–116. https://doi.org/10.1080/10934529.2011.627036.

    Article  CAS  Google Scholar 

  6. Kolpin DW, Furlong ET, Meyer MT, Thurman EM, Zaugg SD, Barber LB, et al. Pharmaceuticals, hormones, and other organic wastewater contaminants in U.S. streams, 1999-2000: a national reconnaissance. Environ Sci Technol. 2002;36(6):1202–11.

    Article  CAS  PubMed  Google Scholar 

  7. Vasskog T, Anderssen T, Pedersen-Bjergaard S, Kallenborn R, Jensen E. Occurrence of selective serotonin reuptake inhibitors in sewage and receiving waters at Spitsbergen and in Norway. J Chromatogr A. 2008;1185(2):194–205. https://doi.org/10.1016/j.chroma.2008.01.063.

    Article  CAS  PubMed  Google Scholar 

  8. Metcalfe CD, Chu SG, Judt C, Li HX, Oakes KD, Servos MR, et al. Antidepressants and their metabolites in municipal wastewater, and downstream exposure in an urban watershed. Environ Toxicol Chem. 2010;29(1):79–89. https://doi.org/10.1002/etc.27.

    Article  CAS  PubMed  Google Scholar 

  9. Schlüsener MP, Hardenbicker P, Nilson E, Schulz M, Viergutz C, Ternes TA. Occurrence of venlafaxine, other antidepressants and selected metabolites in the Rhine catchment in the face of climate change. Environ Pollut. 2015;196:247–56. https://doi.org/10.1016/j.envpol.2014.09.019.

    Article  CAS  PubMed  Google Scholar 

  10. Tixier C, Singer HP, Oellers S, Müller SR. Occurrence and fate of carbamazepine, clofibric acid, diclofenac, ibuprofen, ketoprofen, and naproxen in surface waters. Environ Sci Technol. 2003;37(6):1061–8. https://doi.org/10.1021/es025834r.

    Article  CAS  PubMed  Google Scholar 

  11. Muñoz I, López-Doval JC, Ricart M, Villagrasa M, Brix R, Geiszinger A, et al. Bridging levels of pharmaceuticals in river water with biological community structure in the Llobregat river basin (northeast Spain). Environ Toxicol Chem. 2009;28(12):2706–14. https://doi.org/10.1897/08-486.1.

    Article  PubMed  Google Scholar 

  12. Valcárcel Y, Martínez F, González-Alonso S, Segura Y, Catalá M, Molina R, et al. Drugs of abuse in surface and tap waters of the Tagus River basin: heterogeneous photo-Fenton process is effective in their degradation. Environ Int. 2012;41(1):35–43. https://doi.org/10.1016/j.envint.2011.12.006.

    Article  CAS  PubMed  Google Scholar 

  13. Bendz D, Paxéus NA, Ginn TR, Loge FJ. Occurrence and fate of pharmaceutically active compounds in the environment, a case study: Höje River in Sweden. J Hazard Mater. 2005;122(3):195–204. https://doi.org/10.1016/j.jhazmat.2005.03.012.

    Article  CAS  PubMed  Google Scholar 

  14. Gunnarsson L, Jauhiainen A, Kristiansson E, Nerman O, Larsson DGJ. Evolutionary conservation of human drug targets in organisms used for environmental risk assessments. Environ Sci Technol. 2008;42(15):5807–13. https://doi.org/10.1021/es8005173.

    Article  CAS  PubMed  Google Scholar 

  15. Brodin T, Fick J, Jonsson M, Klaminder J. Dilute concentrations of a psychiatric drug alter behavior of fish from natural populations. Science. 2013;339(6121):814–5. https://doi.org/10.1126/science.1226850.

    Article  CAS  PubMed  Google Scholar 

  16. Fong PP, Ford AT. The biological effects of antidepressants on the molluscs and crustaceans: a review. Aquat Toxicol. 2014;151:4–13. https://doi.org/10.1016/j.aquatox.2013.12.003.

    Article  CAS  PubMed  Google Scholar 

  17. Ford AT, Fong PP. The effects of antidepressants appear to be rapid and at environmentally relevant concentrations. Environ Toxicol Chem. 2016;35(4):794–8. https://doi.org/10.1002/etc.3087.

    Article  CAS  PubMed  Google Scholar 

  18. Rivetti C, Campos B, Barata C. Low environmental levels of neuro-active pharmaceuticals alter phototactic behaviour and reproduction in Daphnia magna. Aquat Toxicol. 2016;170:289–96. https://doi.org/10.1016/j.aquatox.2015.07.019.

    Article  CAS  PubMed  Google Scholar 

  19. Rivetti C, Campos B, Piña B, Raldúa D, Kato Y, Watanabe H, et al. Tryptophan hydroxylase (TRH) loss of function mutations induce growth and behavioral defects in Daphnia magna. Sci Rep. 2018;8(1):1518. https://doi.org/10.1038/s41598-018-19778-0.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Gómez-Canela C, Tornero-Cañadas D, Prats E, Piña B, Tauler R, Raldúa D. Comprehensive characterization of neurochemicals in three zebrafish chemical models of human acute organophosphorus poisoning using liquid chromatography-tandem mass spectrometry. Anal Bioanal Chem. 2018;410(6):1735–48. https://doi.org/10.1007/s00216-017-0827-3.

    Article  CAS  PubMed  Google Scholar 

  21. Kim TH, Choi J, Kim HG, Kim HR. Quantification of neurotransmitters in mouse brain tissue by using liquid chromatography coupled electrospray tandem mass spectrometry. J Anal Methods Chem. 2014;2014(506870). https://doi.org/10.1155/2014/506870.

  22. Tufi S, Lamoree M, de Boer J, Leonards P. Simultaneous analysis of multiple neurotransmitters by hydrophilic interaction liquid chromatography coupled to tandem mass spectrometry. J Chromatogr A. 2015;1395:79–87. https://doi.org/10.1016/j.chroma.2015.03.056.

    Article  CAS  PubMed  Google Scholar 

  23. Zhou W, Zhu B, Liu F, Lyu C, Zhang S, Yan C, et al. Wei H; A rapid and simple method for the simultaneous determination of four endogenous monoamine neurotransmitters in rat brain using hydrophilic interaction liquid chromatography coupled with atmospheric-pressure chemical ionization tandem mass spectrometry. J Chromatogr B. 2015;1002:379–86. https://doi.org/10.1016/j.jchromb.2015.08.042.

    Article  CAS  Google Scholar 

  24. Wang H, Chung-Davidson YW, Li K, Scott AM, Li W. Quantification of monoamine neurotransmitters and melatonin in sea lamprey brain tissues by high performance liquid chromatography-electrospray ionization tandem mass spectrometry. Talanta. 2012;89:383–90. https://doi.org/10.1016/j.talanta.2011.12.048.

    Article  CAS  PubMed  Google Scholar 

  25. Park JY, Myung SW, Kim IS, Choi DK, Kwon SJ, Yoon SH. Simultaneous measurement of serotonin, dopamine and their metabolites in mouse brain extracts by high-performance liquid chromatography with mass spectrometry following derivatization with ethyl chloroformate. Biol Pharm Bull. 2013;36(2):252–8. https://doi.org/10.1248/bpb.b12-00689.

    Article  CAS  PubMed  Google Scholar 

  26. van de Merbel NC. Quantitative determination of endogenous compounds in biological samples using chromatographic techniques. Trends Anal Chem. 2008;27(10):924–33. https://doi.org/10.1016/j.trac.2008.09.002.

    Article  CAS  Google Scholar 

  27. Barata C, Baird DJ. Determining the ecotoxicological mode of action of toxicants from measurements on individuals: results from short duration chronic tests with Daphnia magna Straus. Aquat Toxicol. 2000;48:195–209.

    Article  CAS  PubMed  Google Scholar 

  28. American Society for Testing and Materials. Standard guide for conducting renewal life - cycle toxicity tests with Daphnia magna. In: Annual book of ASTM standards. Philadelphia: American Society for Testing and Materials. 1994;1994:512–8.

  29. Bicker J, Fortuna A, Alves G, Falcão A. Liquid chromatographic methods for the quantification of catecholamines and their metabolites in several biological samples - a review. Anal Chim Acta. 2013;768(1):12–34. https://doi.org/10.1016/j.aca.2012.12.030.

    Article  CAS  PubMed  Google Scholar 

  30. González RR, Fernández RF, Vidal JLM, Frenich AG, Pérez MLG. Development and validation of an ultra-high performance liquid chromatography-tandem mass-spectrometry (UHPLC-MS/MS) method for the simultaneous determination of neurotransmitters in rat brain samples. J Neurosci Methods. 2011;198(2):187–94. https://doi.org/10.1016/j.jneumeth.2011.03.023.

    Article  CAS  PubMed  Google Scholar 

  31. Wojnicz A, Avendaño Ortiz J, Casas AI, Freitas AE, G. López M, Ruiz-Nuño A. Simultaneous determination of 8 neurotransmitters and their metabolite levels in rat brain using liquid chromatography in tandem with mass spectrometry: application to the murine Nrf2 model of depression. Clin Chim Acta. 2016;453:174–181. https://doi.org/10.1016/j.cca.2015.12.023.

  32. Yang ZL, Li H, Wang B, Liu SY. An optimized method for neurotransmitters and their metabolites analysis in mouse hypothalamus by high performance liquid chromatography-Q Exactive hybrid quadrupole-orbitrap high-resolution accurate mass spectrometry. J Chromatogr B. 2016;1012–1013:79–88. https://doi.org/10.1016/j.jchromb.2016.01.008.

    Article  CAS  Google Scholar 

  33. European Commission. 2002/657/EC. Commission Decision of 12 August 2002 implementing Council Directive 96/23/EC concerning the performance of analytical methods and the interpretation of results. Off J Eur Communities. 2002;221:8–36.

    Google Scholar 

  34. Van Eeckhaut A, Lanckmans K, Sarre S, Smolders I, Michotte Y. Validation of bioanalytical LC-MS/MS assays: Evaluation of matrix effects. J Chromatagr B. 2009;877(23):2198–207. https://doi.org/10.1016/j.jchromb.2009.01.003.

    Article  CAS  Google Scholar 

  35. Garreta-Lara E, Campos B, Barata C, Lacorte S, Tauler R. Metabolic profiling of Daphnia magna exposed to environmental stressors by GC–MS and chemometric tools. Metabolomics. 2016;12(5):86. https://doi.org/10.1007/s11306-016-1021-x.

    Article  CAS  Google Scholar 

  36. Denno ME, Privman E, Venton BJ. Analysis of neurotransmitter tissue content of drosophila melanogaster in different life stages. ACS Chem Neurosci. 2015;6(1):117–23. https://doi.org/10.1021/cn500261e.

    Article  CAS  PubMed  Google Scholar 

  37. Campos B, Rivetti C, Kress T, Barata C, Dircksen H. Depressing antidepressant: fluoxetine affects serotonin neurons causing adverse reproductive responses in Daphnia magna. Environ Sci Technol. 2016;50(11):6000–7. https://doi.org/10.1021/acs.est.6b00826.

    Article  CAS  PubMed  Google Scholar 

  38. McCoole MD, Baer KN, Christie AE. Histaminergic signaling in the central nervous system of Daphnia and a role for it in the control of phototactic behavior. J Exp Biol. 2011;214(10):1773–82. https://doi.org/10.1242/jeb.054486.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Jeong TY, Kim HY, Kim SD. Multi-generational effects of propranolol on Daphnia magna at different environmental concentrations. Environ Pollut. 2015;206:188–94. https://doi.org/10.1016/j.envpol.2015.07.003.

    Article  CAS  PubMed  Google Scholar 

  40. Simão FCP, Martínez-Jerónimo F, Blasco V, Moreno F, Porta JM, Pestana JLT, et al. Using a new high-throughput video-tracking platform to assess behavioural changes in Daphnia magna exposed to neuro-active drugs. Sci Total Environ. 2019;662:160–7. https://doi.org/10.1016/j.scitotenv.2019.01.187.

    Article  CAS  PubMed  Google Scholar 

  41. Tolou-Ghamari Z, Zare M, Habibabadi JM, Najafi MR. A quick review of carbamazepine pharmacokinetics in epilepsy from 1953 to 2012. J Res Med Sci. 2013;18(Suppl 1):S81–5.

    PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

CR thanks the Spanish Ministerio de Economía y Competitividad (MINECO) for a PhD fellowship (BES-2012-053631).

Funding

This study received funding from the Ministerio de Economía y Competitividad (MINECO) (reference nos. CTM2014-51985-R and CTM2017-83242-R).

Author information

Authors and Affiliations

  1. Department of Environmental Chemistry, IDAEA-CSIC, Jordi Girona 18-26, 08034, Barcelona, Spain

    Claudia Rivetti, Esther Climent & Carlos Barata

  2. Department of Analytical and Applied Chemistry, School of Engineering, Institut Químic de Sarrià, Universitat Ramon Llull, Via Agusta 390, 08017, Barcelona, Spain

    Cristian Gómez-Canela

Authors
  1. Claudia Rivetti
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Esther Climent
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Cristian Gómez-Canela
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Carlos Barata
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Carlos Barata.

Ethics declarations

Conflict of interest

The authors declare that they have no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

ESM 1

(PDF 1.17 mb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Rivetti, C., Climent, E., Gómez-Canela, C. et al. Characterization of neurotransmitter profiles in Daphnia magna juveniles exposed to environmental concentrations of antidepressants and anxiolytic and antihypertensive drugs using liquid chromatography–tandem mass spectrometry. Anal Bioanal Chem 411, 5867–5876 (2019). https://doi.org/10.1007/s00216-019-01968-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00216-019-01968-y

Keywords

Search

Navigation