Methylenedioxypryovalerone (MDPV) Rapidly Increases Dopamine Transporter and Vesicular Monoamine Transporter‐2 Function

Abstract

Methylenedioxypyrovalerone (MDPV) is a synthetic cathinone designer drug primarily abused for its psychostimulant properties. Rapid dysregulation of central monoamine neurotransmitter transport into presynaptic terminals and synaptic vesicles are principal mechanisms of psychostimulant action, and contribute to the development of persistent monoaminergic deficits. Still, the impact of in vivo MDPV administration on the function of central monoamine transporters is not fully elucidated. Consequently, this study examined the response of the striatal dopamine transporter (DAT) and vesicular monoamine transporter‐2 (VMAT2) to a single MDPV exposure in adult male rats. A single in vivo MDPV administration rapidly (within 1 h) and reversibly (effect diminishes after 6 h) increased both DAT and VMAT2 function when assessed ex vivo in striatal synaptosomes and non‐membrane‐associated (presumably cytoplasmic) synaptic vesicles, respectively. MDPV treatment did not increase VMAT2 immunoreactivity within the cytoplasmic synaptic vesicle fraction, suggesting increased VMAT2 activity is unlikely due to intracellular trafficking increasing the number of available cytoplasmic VMAT2‐associated synaptic vesicles. In contrast to other psychostimulants, most notably methamphetamine and methylphenidate, MDPV acutely increases both DAT and VMAT2 function, and increased VMAT2 function is likely independent of vesicular trafficking‐mediated mechanisms. Together, these data suggest that MDPV has a unique and undescribed mechanism of action on striatal dopaminergic neurons.Support or Funding InformationThis work was supported by National Institutes of Health grants DA039145 and DA031883.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.