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Atypical dopamine efflux caused by3,4-methylenedioxypyrovalerone (MDPV) via the human dopamine transporter

Shekar, A and Aguilar, JI and Galli, G and Cozzi, NV and Brandt, SD and Ruoho, AE and Baumann, MH and Matthies, HJG and Galli, A (2017) Atypical dopamine efflux caused by3,4-methylenedioxypyrovalerone (MDPV) via the human dopamine transporter. Journal of Chemical Neuroanatomy. ISSN 0891-0618

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Abstract

Synthetic cathinones are similar in chemical structure to amphetamines, and their behavioral effects are associated with enhanced dopaminergic signaling. The past ten years of research on the common constituent of bath salts, MDPV (the synthetic cathinone 3,4-methylenedioxypyrovalerone), has aided the understanding of how synthetic cathinones act at the dopamine (DA) transporter (DAT). Several groups have described the ability of MDPV to block the DAT with high-affinity. In this study, we demonstrate for the first time, a new mode of action of MDPV, namely its ability to promote DAT-mediated DA efflux. Using single cell amperometric assays, we determined that low concentrations of MDPV (1 nM) can cause reverse transport of DA via DAT. Notably, administration of MDPV leads to hyperlocomotion in Drosophila melanogaster. These data describe further how MDPV acts at the DAT possibly paving the way for novel treatment strategies for individuals who abuse bath salts.

Item Type: Article
Uncontrolled Keywords: 1109 Neurosciences
Subjects: Q Science > QD Chemistry
R Medicine > RM Therapeutics. Pharmacology
Divisions: Pharmacy & Biomolecular Sciences
Publisher: Elsevier BV
Date Deposited: 25 Jan 2017 11:13
Last Modified: 07 Sep 2017 13:02
DOI or Identification number: 10.1016/j.jchemneu.2017.01.004
URI: http://researchonline.ljmu.ac.uk/id/eprint/5359

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