Abstract
The abuse of psychoactive ‘bath salts’ containing cathinones such as 3,4-methylenedioxypyrovalerone (MDPV) is a growing public health concern, yet little is known about their pharmacology. Here, we evaluated the effects of MDPV and related drugs using molecular, cellular, and whole-animal methods. In vitro transporter assays were performed in rat brain synaptosomes and in cells expressing human transporters, while clearance of endogenous dopamine was measured by fast-scan cyclic voltammetry in mouse striatal slices. Assessments of in vivo neurochemistry, locomotor activity, and cardiovascular parameters were carried out in rats. We found that MDPV blocks uptake of [3H]dopamine (IC50=4.1 nM) and [3H]norepinephrine (IC50=26 nM) with high potency but has weak effects on uptake of [3H]serotonin (IC50=3349 nM). In contrast to other psychoactive cathinones (eg, mephedrone), MDPV is not a transporter substrate. The clearance of endogenous dopamine is inhibited by MDPV and cocaine in a similar manner, but MDPV displays greater potency and efficacy. Consistent with in vitro findings, MDPV (0.1–0.3 mg/kg, intravenous) increases extracellular concentrations of dopamine in the nucleus accumbens. Additionally, MDPV (0.1–3.0 mg/kg, subcutaneous) is at least 10 times more potent than cocaine at producing locomotor activation, tachycardia, and hypertension in rats. Our data show that MDPV is a monoamine transporter blocker with increased potency and selectivity for catecholamines when compared with cocaine. The robust stimulation of dopamine transmission by MDPV predicts serious potential for abuse and may provide a mechanism to explain the adverse effects observed in humans taking high doses of ‘bath salts’ preparations.
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Acknowledgements
We thank Mario A. Ayestas Jr. for helpful technical assistance. This research was generously supported by the Intramural Research Program of the National Institute on Drug Abuse, National Institutes of Health, USA, and by the Austrian Science Fund/FWF, SFB3506. The views expressed herein are those of the authors and do not necessarily represent the views of the Drug Enforcement Administration, the United States Department of Justice or an officer or entity of the United States.
Author contributions
MHB designed and supervised the project, analyzed data, and wrote the first draft of the manuscript. NVC and SDB synthesized and characterized the identity and purity of MDPV, mephedrone, and methylone. JSP, MHB, and RBR designed, carried out, and analyzed the uptake and release experiments. MH and HHS designed and performed efflux experiments in HEK cells. AFH and CRL designed, carried out, and analyzed the cyclic voltammetry studies. KRL and MHB designed and performed microdialysis experiments. EFT, CWS, and SRG designed, carried out, and analyzed the locomotor activity studies. EFT, SRT, and CWS designed, performed, and analyzed the telemetry experiments. All authors contributed significantly to the writing of the final version of the article.
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Baumann, M., Partilla, J., Lehner, K. et al. Powerful Cocaine-Like Actions of 3,4-Methylenedioxypyrovalerone (MDPV), a Principal Constituent of Psychoactive ‘Bath Salts’ Products. Neuropsychopharmacol 38, 552–562 (2013). https://doi.org/10.1038/npp.2012.204
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DOI: https://doi.org/10.1038/npp.2012.204
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