Neurotoxicity screening of (illicit) drugs using novel methods for analysis of microelectrode array (MEA) recordings

NeuroToxicology

Volumn 55, Issue , 2016, Pages 1-9

  Hondebrink, L ^a   Verboven, A H A ^b   Drega, W S ^b   Schmeink, S ^b   de Groot, M W G D M ^b   van Kleef, R G D M ^b   Wijnolts, F M J ^b   de Groot, A ^b   Meulenbelt, J ^a,b   Westerink, R H S ^b  

^a UNIVERSITY MEDICAL CENTER UTRECHT   (Netherlands)

^b UTRECHT UNIVERSITY   (Netherlands)

Author keywords

Analysis strategy; Characterisation; Illicit drugs; Integrated testing strategy; Neurotoxicity screening

Indexed keywords

(3 CHLOROPHENYL)PIPERAZINE; 3,4 METHYLENEDIOXYMETHAMPHETAMINE; 4 AMINOBUTYRIC ACID; 4 FLUOROAMPHETAMINE; 6 CYANO 7 NITRO 2,3 QUINOXALINEDIONE; ACETYLCHOLINE; BICUCULLINE; DIAZEPAM; DIZOCILPINE; DOPAMINE; GLUTAMIC ACID; ILLICIT DRUG; METHOXETAMINE; NEUROTRANSMITTER; NICOTINE; SEROTONIN; UNCLASSIFIED DRUG; 4 AMINOBUTYRIC ACID CARRIER; AMINO ACID RECEPTOR BLOCKING AGENT; DIZOCILPINE MALEATE; GABAERGIC RECEPTOR AFFECTING AGENT; GLIAL FIBRILLARY ACIDIC PROTEIN; STREET DRUG; TYROSINE 3 MONOOXYGENASE; VESICULAR GLUTAMATE TRANSPORTER 1;

ANIMAL CELL; ANIMAL TISSUE; ARTICLE; ASTROCYTE; BRAIN NERVE CELL; CONTROLLED STUDY; FALSE NEGATIVE RESULT; GABAERGIC SYSTEM; GLUTAMATERGIC SYNAPSE; HEALTH HAZARD; IC50; MICROARRAY ANALYSIS; MICROELECTRODE; MULTIWELL MICROELECTRODE ARRAY; NEUROTOXICITY; NONHUMAN; PRIORITY JOURNAL; RAT; RISK ASSESSMENT; ACTION POTENTIAL; ANIMAL; BRAIN CORTEX; CYTOLOGY; DRUG EFFECTS; METABOLISM; NERVE CELL; NEWBORN; PRECLINICAL STUDY; PROCEDURES; TIME FACTOR; WISTAR RAT;

6-CYANO-7-NITROQUINOXALINE-2,3-DIONE; ACTION POTENTIALS; ANIMALS; ANIMALS, NEWBORN; ASTROCYTES; CEREBRAL CORTEX; DIZOCILPINE MALEATE; DRUG EVALUATION, PRECLINICAL; EXCITATORY AMINO ACID ANTAGONISTS; GABA AGENTS; GABA PLASMA MEMBRANE TRANSPORT PROTEINS; GLIAL FIBRILLARY ACIDIC PROTEIN; MICROELECTRODES; NEURONS; RATS; RATS, WISTAR; STREET DRUGS; TIME FACTORS; TYROSINE 3-MONOOXYGENASE; VESICULAR GLUTAMATE TRANSPORT PROTEIN 1;

EID: 84965075992     PISSN: 0161813X     EISSN: 18729711     Source Type: Journal    
DOI: 10.1016/j.neuro.2016.04.020     Document Type: Article

References (41)

1. Abe E., Ricard F., Darrouzain F., Alvarez J.C. An automated method for measurement of methoxetamine in human plasma by use of turbulent flow on-line extraction coupled with liquid chromatography and mass spectrometric detection. Anal. Bioanal. Chem. 2013, 405(1):239-245.
2. Bal-Price A.K., Sunõl C., Weiss D.G., van Vliet E., Westerink R.H.S., Costa L.G. Application of in vitro neurotoxicity testing for regulatory purposes: symposium III summary and research needs. Neurotoxicology 2008, 29:520-531.
3. Bal-Price A.K., Hogberg H.T., Buzanska L., Coecke S. Relevance of in vitro neurotoxicity testing for regulatory requirements: challenges to be considered. Neurotoxicol. Teratol. 2010, 32:36-41.
4. de Groot M.W.G.D.M., van Kleef R.G., de Groot A., Westerink R.H.S. In vitro developmental neurotoxicity following chronic exposure to 50 Hz extremely low frequency electromagnetic fields (ELF-EMF) in primary rat cortical cultures. Toxicol. Sci. 2016, 149:433-440.
5. DeVane C.L., Boulton D.W., Miller L.F., Miller R.L. Pharmacokinetics of trazodone and its major metabolite m-chlorophenylpiperazine in plasma and brain of rats. Int. J. Neuropsychopharmacol. 1999, 2:17-23.
6. Flash Eurobarometer 330, 2011. Young attitudes on drugs. Analytical report. Survey conducted by The Gallup Organization, Hungary upon the request of Directorate-General Justice. Available at: (accessed 11.09.15.). http://www.drugsandalcohol.ie/22196/13/Eurobarometer%20401%20Young%20people%20and%20drugs%20-%20full%20report.pdf.
7. Flash Eurobarometer 401, 2014. Young people and drugs. Report. Conducted by TNS Political & Social at the request of the European Commission, Directorate-General for Justice. Available at: (accessed 11.09.15.). http://www.drugsandalcohol.ie/22196/13/Eurobarometer%20401%20Young%20people%20and%20drugs%20-%20full%20report.pdf.
8. Gross G.W., Rhoades B.K. The use of neuronal networks on multielectrode arrays as biosensors. Biosens. Bioelectron. 1995, 10:553-567.
9. Herrero M.T., Oset-gasque M.J., Canadas S., Vicente S., González M.P. Effect of various depolarizing agents on endogenous amino acid neurotransmitter release in rat cortical neurons in culture. Neurochem. Int. 1998, 32(3):257-264.
10. Hogberg H.T., Sobanski T., Novellino A., Whelan M., Weiss D.G., Bal-Price A.K. Application of micro-electrode arrays (MEAs) as an emerging technology for developmental neurotoxicity: evaluation of domoic acid-induced effects in primary cultures of rat cortical neurons. Neurotoxicology 2011, 32:158-168.
11. Hondebrink L., Meulenbelt J., Timmerman J.G., van den Berg M., Westerink R.H.S. Amphetamine reduces vesicular dopamine content in dexamethasone-differentiated PC12 cells only following L-DOPA exposure. J. Neurochem. 2009, 111(2):624-633.
12. A receptor function: a novel mode of action of drugs of abuse. Neurotoxicology 2011, 32(6):823-827.
13. Hondebrink L., Meulenbelt J., Rietjens S.J., Meijer M., Westerink R.H.S. Methamphetamine, amphetamine, MDMA ('ecstasy'), MDA and mCPP modulate electrical and cholinergic input in PC12 cells. Neurotoxicology 2012, 33:255-260.
14. A receptors by mixtures of commonly used drugs of abuse. Neurotoxicology 2013, 35:23-29.
15. Hondebrink L., Hermans E.J., Schmeink S., van Kleef R.G., Meulenbelt J., Westerink R.H.S. Structure-dependent inhibition of the human α1β2γ2 GABAA receptor by piperazine derivatives: a novel mode of action. Neurotoxicology 2015, 51:1-9.
16. International Conference on Harmonisation (ICH), 2000. Safety Pharmacology Studies for Human Pharmaceuticals. ICH S7A. International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use, Geneva. CPMP/ICH/539/00-ICH S7A. http://www.fda.gov/CBER/gdlns/ichs7a071201.htm.
17. Imbert L., Boucher A., Delhome G., Cueto T., Boudinaud M., Maublanc J., Dulaurent S., Descotes J., Lachâtre G., Gaulier J.M. Analytical findings of an acute intoxication after inhalation of methoxetamine. J. Anal. Toxicol. 2014, 38(7):410-415.
18. Johnstone A.F.M., Gross G.W., Weiss D.G., Schroeder O.H., Gramowski A., Shafer T.J. Microelectrode arrays: a physiologically based neurotoxicity testing platform for the 21st century. Neurotoxicology 2010, 31:331-350.
19. Kahn R.S., Wetzler S., Asnis G.M., Kling M.A., Suckow R.F., van Praag H.M. Effects of m-chlorophenylpiperazine in normal subjects: a dose-response study. Psychopharmacology (Berl.) 1990, 100(3):339-344.
20. Klaassen T., Ho Pian K.L., Westenberg H.G., den Boer J.A., van Praag H.M. Serotonin syndrome after challenge with the 5-HT agonist meta-chlorophenylpiperazine. Psychiatry Res. 1998, 79(3):207-212.
21. Łukasik-Głebocka M., Sommerfeld K., Tezyk A., Zielińska-Psuja B., Druzdz A. Acute methoxetamine intoxication-a case report with serum and urine concentrations. Przegl. Lek. 2013, 70(8):671-673.
22. Lefew W.R., McConnell E.R., Crooks J.L., Shafer T.J. Evaluation of microelectrode array data using Bayesian modeling as an approach to screening and prioritization for neurotoxicity testing. Neurotoxicology 2013, 36:34-41. 10.1016/j.neuro.2013.02.006.
23. Mack C.M., Lin B.J., Turner J.D., Johnstone A.F., Burgoon L.D., Shafer T.J. Burst and principal components analyses of MEA data for 16 chemicals describe at least three effects classes. Neurotoxicology 2014, 40:75-85.
24. Massobrio P., Tessadori J., Chiappalone M., Ghirardi M. In vitro studies of neuronal networks and synaptic plasticity in invertebrates and in mammals using multielectrode arrays. Neural Plast. 2015, 196195. 10.1155/2015/196195.
25. McConnell E.R., McClain M.A., Ross J., LeFew W.R., Shafer T.J. Evaluation of multi-well microelectrode arrays for neurotoxicity screening using a chemical training set. Neurotoxicology 2012, 33:1048-1057.
26. Miller R.L., DeVane C.L. Analysis of trazodone and m-chlorophenylpiperazine in plasma and brain tissue by high-performance liquid chromatography. J. Chromatogr. 1986, 374:388-393.
27. Nicolas J., Hendriksen P.J.M., van Kleef R.G.D.M., de Groot A., Bovee T.F.H., Rietjens I.M.C.M., Westerink R.H.S. Detection of marine neurotoxins in food safety testing using a multielectrode array. Mol. Nutr. Food Res. 2014, 58:2369-2378.
28. Nugteren-van Lonkhuyzen J.J., van Riel A.J.H.P., Brunt T.M., Hondebrink L. Pharmacokinetics, pharmacodynamics and toxicology of frequently detected new psychoactive substances (NPS); 2C-B, 4-fluoroamphetamine and benzofurans. Drug Alcohol Depend. 2015, 157:18-27.
29. OECD, 1997. OECD guideline for the testing of chemicals. Section 4 Health effects, Test No 424: Neurotoxicity Study in Rodents. http://www.oecd-ilibrary.org/environment/test-no-424-neurotoxicity-study-in-rodents_9789264071025-en.
30. Obien M.E.J., Deligkaris K., Bullmann T., Bakkum D.J., Frey U. Revealing neuronal function through microelectrode array recordings. Front. Neurosci. 2015, 8:423. 10.3389/fnins.2014.00423.
31. Puia G., Gullo F., Dossi E., Lecchi M., Wanke E. Novel modulatory effects of neurosteroids and benzodiazepines on excitatory and inhibitory neurons excitability: a multi-electrode array recording study. Front. Neural Circuits 2012, 6(94):1-17.
32. Rickli A., Hoener M.C., Liechti M.E. Monoamine transporter and receptor interaction profiles of novel psychoactive substances: para-halogenated amphetamines and pyrovalerone cathinones. Eur. Neuropsychopharmacol. 2015, 25(3):365-376.
33. Roth B.L., Gibbons S., Arunotayanun W., Huang X.P., Setola V., Treble R., Iversen L. The ketamine analogue methoxetamine and 3- and 4-methoxy analogues of phencyclidine are high affinity and selective ligands for the glutamate NMDA receptor. PLoS One 2013, 8(3):e59334.
34. Shields J.E., Dargan P.I., Wood D.M., Puchnarewicz M., Davies S., Waring W.S. Methoxetamine associated reversible cerebellar toxicity: three cases with analytical confirmation. Clin. Toxicol. 2012, 50(5):438-440.
35. Simmler L.D., Rickli A., Schramm Y., Hoener M.C., Liechti M.E. Pharmacological profiles of aminoindanes, piperazines, and pipradrol derivatives. Biochem. Pharmacol. 2014, 88:237-244.
36. Smith T.M., Suckow R.F. Trazodone and m-chlorophenylpiperazine. Concentration in brain and receptor activity in regions in the brain associated with anxiety. Neuropharmacology 1985, 24(11):1067-1071.
37. Steidl E.M., Neveu E., Bertrand D., Buisson B. The adult rat hippocampal slice revisited with multi-electrode arrays. Brain Res. 2006, 1096(1):70-84.
38. Valdivia P., Martin M., LeFew W.R., Ross J., Houck K.A., Shafer T.J. Multi-well microelectrode array recordings detect neuroactivity of ToxCast compounds. Neurotoxicology 2014, 44:204-217.
39. Wallace K., Strickland J.D., Valdivia P., Mundy W.R., Shafer T.J. A multiplexed assay for determination of neurotoxicant effects on spontaneous network activity and viability from microelectrode arrays. Neurotoxicology 2015, 49:79-85. 10.1016/j.neuro.2015.05.007.
40. Wood D., Cottrell A., Baker S.C., Southgate J., Harris M., Fulford S., Woodhouse C., Gillatt D. Recreational ketamine: from pleasure to pain. BJU Int. 2011, 107:1881-1884.
41. World Drug Report, 2015. United Nations Office on Drugs and Crime, United Nations publication, Sales No. E.15. XI.6. (accessed 15.09.15.). http://www.unodc.org/unodc/en/drug-prevention-and-treatment/index.html.