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Effects of MDPV on dopamine transporter regulation in male rats. Comparison with cocaine

  • Raul Lopez-Arnau
  • Leticia Duart-Castells
  • Barbara Aster
  • Jorge Camarasa
  • Elena Escubedo
  • David Pubill
Original Investigation

Abstract

Rationale

MDPV (3,4-methylenedioxypyrovalerone) is a synthetic cathinone present in bath salts. It is a powerful psychostimulant and blocker of the dopamine transporter (DAT), like cocaine. It is known that acute exposure to psychostimulants induces rapid changes in DAT function.

Objectives

To investigate the effects of MDPV on DAT function comparing with cocaine.

Methods

Binding of [3H]WIN 35428 was performed on PC 12 cells treated with MDPV and washed. Rat striatal synaptosomes were incubated with MDPV or cocaine (1 μM) for 1 h and [3H]dopamine (DA) uptake was performed. Also, different treatments with MDPV or cocaine were performed in Sprague-Dawley rats to assess locomotor activity and ex vivo [3H]DA uptake.

Results

MDPV increased surface [3H]WIN 35428 binding on PC 12 cells. In vitro incubation of synaptosomes with MDPV produced significant increases in Vmax and KM for [3H]DA uptake. In synaptosomes from MDPV- (1.5 mg/kg, s.c.) and cocaine- (30 mg/kg, i.p.) treated rats, there was a significantly higher and more persistent increase in [3H]DA uptake in the case of MDPV than cocaine. Repeated doses of MDPV developed tolerance to this DAT upregulation and 24 h after the 5-day treatment with MDPV, [3H]DA uptake was reduced. However, a challenge with the same drugs after withdrawal recovered the DAT upregulation by both drugs and showed an increased response to MDPV vs the first dose. At the same time, animals were sensitized to the stereotypies induced by both psychostimulants.

Conclusions

MDPV induces a rapid and reversible functional upregulation of DAT more powerfully and lasting than cocaine.

Keywords

Bath salts Cathinones Cocaine Dopamine transporter Dopamine uptake MDPV Upregulation 

Notes

Acknowledgments

We are grateful to Dr. Anthony L. Riley for helpful critical reading of the manuscript. We also acknowledge Nacho Fargas for eventual technical support.

Funding information

This study was supported by grants from Ministerio de Economia y Competitividad (grant SAF2016-75347R) and Plan Nacional sobre Drogas #2014I020, #2016I004). LDC received FPU grants from the Ministerio de Economía y Competitividad (15/02492). JC, LDC, EE, RLA, and DP belong to the quality mentioned group 2017SGR979 by Generalitat de Catalunya. RLA position was funded by an institutional program of the Universitat de Barcelona in collaboration with Obra Social de la Fundació Bancària La Caixa.

Compliance with ethical standards

The experimental protocols concerning the use of animals in this work were approved by the Animal Ethics Committee of the University of Barcelona under supervision of the Autonomous Government of Catalonia, following the guidelines of the European Communities Council (86/609/EEC).

Conflict of interest

The authors declare that there is no conflict of interest.

Supplementary material

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Supplementary Figure 1

(PNG 365 kb)

213_2018_5052_MOESM1_ESM.tif (328 kb)
High Resolution Image (TIF 328 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Pharmacology, Toxicology and Therapeutic Chemistry, Pharmacology Section and Institute of Biomedicine (IBUB), Faculty of PharmacyUniversity of BarcelonaBarcelonaSpain

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