Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 391, Issue 3, pp 247–254 | Cite as

Effect of the combination of mephedrone plus ethanol on serotonin and dopamine release in the nucleus accumbens and medial prefrontal cortex of awake rats

  • Raúl López-Arnau
  • Mario Buenrostro-Jáuregui
  • Jorge Camarasa
  • David Pubill
  • Elena Escubedo
Brief Communication


Cathinones, such as mephedrone (Meph), are often co-abused with alcoholic drinks. In the present study, we investigated the combined effects of Meph plus ethanol (EtOH) on neurotransmitter release in the nucleus accumbens (NAc) and the medial prefrontal cortex (mPFC). A guide canula was stereotaxically implanted into either the NAc or the mPFC of male Sprague-Dawley rats. Seven days after surgery, a microdialysis probe was inserted and rats were administered saline, EtOH (1 g/kg, i.p.), Meph (25 mg/kg, s.c.), or their combination, and dialysates were collected. Serotonin (5-HT), dopamine (DA), and their metabolites (5-HIAA, DOPAC and HVA) were determined through high-pressure liquid chromatography coupled to mass spectrometry. 5-HT and DA peaked 40 min after Meph administration (with or without EtOH co-treatment) in both areas. EtOH combined with Meph increased the 5-HT release compared with the rats receiving Meph alone (85% in NAc, 65% in mPFC), although the overall change in the area under the curve only reached statistical significance in the NAc. In mPFC, the increased release of 5-HT lasted longer in the combination than that in the Meph group. Moreover, EtOH potentiated the psychostimulant effect of Meph measured as a locomotor activity. Given that both 5-HT and DA are also related with reward and impulsivity, the observed effects point to an increased risk of abuse liability when combining Meph with EtOH compared with consuming these drugs alone.


Mephedrone Ethanol Cathinones Microdialysis Drug polyabuse Bath salts 



5-Hydroxyindoleacetic acid






3,4-Dihydroxyphenylacetic acid




Liquid chromatography-mass spectrometry






Medial prefrontal cortex


Nucleus accumbens



This work was supported by grants from “Plan Nacional sobre Drogas” (2012I102) and from “Plan Nacional de Investigación Científica” (SAF2013-46135-P). Our group holds the quality mention from the “Generalitat de Catalunya” (2014SGR1081). None of the funding sources had further role in study design, collection, analysis, and interpretation of data, in the writing of the report and in the decision to submit the paper for publication. R. López-Arnau 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

All animal care and experimental protocols in this study complied with the guidelines of the European Community Council (86/609/ECC) and were approved by the Animal Ethics Committee of the University of Barcelona. All efforts were made to minimize animal suffering and to reduce the number of animals used.

Conflict of interest

The authors declare that they have no conflict of interest.


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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
  2. 2.Neuroscience Laboratory, Department of PsychologyUniversidad IberoamericanaMexico CityMexico

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