From the Cover: Zebrafish Larvae Are Insensitive to Stimulation by Cocaine: Importance of Exposure Route and Toxicokinetics.

Autor:	Kirla KT; Department of Forensic Pharmacology and Toxicology, University of Zurich, Zurich Institute of Forensic Medicine, Zurich, 8057, Switzerland.; Department of Environmental Toxicology, Eawag, Swiss Federal Institute of Aquatic Science and Technology, Duebendorf, 8600, Switzerland., Groh KJ; Department of Environmental Toxicology, Eawag, Swiss Federal Institute of Aquatic Science and Technology, Duebendorf, 8600, Switzerland., Steuer AE; Department of Forensic Pharmacology and Toxicology, University of Zurich, Zurich Institute of Forensic Medicine, Zurich, 8057, Switzerland., Poetzsch M; Department of Forensic Pharmacology and Toxicology, University of Zurich, Zurich Institute of Forensic Medicine, Zurich, 8057, Switzerland., Banote RK; Department of Psychiatry and Neurochemistry, University of Gothenburg, The Sahlgrenska Academy, Institute of Neuroscience and Physiology, Gothenburg, S-41345, Sweden., Stadnicka-Michalak J; Department of Environmental Toxicology, Eawag, Swiss Federal Institute of Aquatic Science and Technology, Duebendorf, 8600, Switzerland.; EPFL, School of Architecture, Civil and Environmental Engineering, Lausanne, 1015, Switzerland., Eggen RI; Department of Environmental Toxicology, Eawag, Swiss Federal Institute of Aquatic Science and Technology, Duebendorf, 8600, Switzerland.; ETHZ, Institute of Biogeochemistry and Pollutant Dynamics, Zurich, 8092, Switzerland., Schirmer K; Department of Environmental Toxicology, Eawag, Swiss Federal Institute of Aquatic Science and Technology, Duebendorf, 8600, Switzerland kristin.schirmer@eawag.ch.; EPFL, School of Architecture, Civil and Environmental Engineering, Lausanne, 1015, Switzerland.; ETHZ, Institute of Biogeochemistry and Pollutant Dynamics, Zurich, 8092, Switzerland., Kraemer T; Department of Forensic Pharmacology and Toxicology, University of Zurich, Zurich Institute of Forensic Medicine, Zurich, 8057, Switzerland.
Jazyk:	angličtina
Zdroj:	Toxicological sciences : an official journal of the Society of Toxicology [Toxicol Sci] 2016 Nov; Vol. 154 (1), pp. 183-193. Date of Electronic Publication: 2016 Aug 11.
DOI:	10.1093/toxsci/kfw156
Abstrakt:	Zebrafish (Danio rerio) larvae have been suggested as vertebrate model to complement or even replace mammals for rapidly assessing behavioral effects of psychoactive drugs. Yet, divergent responses have been reported in mammals and fish despite the conservation of many drug targets. Cocaine, eg, acts as stimulant in mammals but no such response has been documented for zebrafish larvae. We hypothesized that differences in exposure routes (inhalation or injection in mammals vs waterborne in fish) may be a reason for differences in behavioral responses. We characterized cocaine toxicokinetics by liquid chromatography-mass spectrometry and found its rapid uptake into larvae. We used Matrix-assisted laser desorption ionization-mass spectrometry imaging for the first time to characterize internal distribution of cocaine in zebrafish larvae. Surprisingly, eyes accumulated the highest amount of cocaine and retained most of it even after 48 h depuration. We attribute this to trapping by pigment melanin, a thus far little explored mechanism that may also be relevant for other basic drugs. Cocaine also reached the brain but with levels similar to those in trunk indicating simple passive diffusion as means of distribution which was supported by toxicokinetic models. Although brain levels covered those known to cause hyperactivity in mammals, only hypoactivity (decreased locomotion) was recorded in zebrafish larvae. Our results therefore point to cocaine's anesthetic properties as the dominant mechanism of interaction in the fish: upon entry through the fish skin and gills, it first acts on peripheral nerves rapidly overriding any potential stimulatory response in the brain. (© The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
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