Atypical dopamine efflux caused by 3,4-methylenedioxypyrovalerone (MDPV) via the human dopamine transporter.
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 (1nM) 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.
Department of Pharmacology, Vanderbilt University, Nashville, TN 37232-8548, United States; Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN 37232-8548, United States; Neuroscience Program in Substance Abuse (N-PISA), Vanderbilt University, Nashville, TN 37232-8548, United States.
Aparna
A
Shekar
Department of Pharmacology, Vanderbilt University, Nashville, TN 37232-8548, United States; Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN 37232-8548, United States; Neuroscience Program in Substance Abuse (N-PISA), Vanderbilt University, Nashville, TN 37232-8548, United States.
Jenny I
JI
Aguilar
University School of Nashville, Nashville, TN 37212, United States.
Greta
G
Galli
Neuropharmacology Laboratory, Department of Cell and Regenerative Biology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, United States.
Nicholas V
NV
Cozzi
School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool L3 3AF, UK.
Simon D
SD
Brandt
Department of Neuroscience, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, United States.
Arnold E
AE
Ruoho
Designer Drug Research Unit (DDRU), Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, United States.
Michael H
MH
Baumann
Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN 37232-8548, United States; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37232-8548, United States.
Heinrich J G
HJG
Matthies
Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN 37232-8548, United States; Neuroscience Program in Substance Abuse (N-PISA), Vanderbilt University, Nashville, TN 37232-8548, United States; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37232-8548, United States. Electronic address: aurelio.galli@vanderbilt.edu.
Aurelio
A
Galli
D000818:Animals; D052117:Benzodioxoles / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000187:drug effects*; D004331:Drosophila melanogaster; D006801:Humans; D011619:Psychotropic Drugs / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology*; D000094982:Synthetic Cathinone
D052117:Benzodioxoles; D050483:Dopamine Plasma Membrane Transport Proteins; D011619:Psychotropic Drugs; D011759:Pyrrolidines; D004298:Dopamine; D000094982:Synthetic Cathinone
3,4-methylenedioxypyrovalerone; Amphetamine; Dopamine transporter; Drosophila