Alcohol enhances the psychostimulant and conditioning effects of mephedrone in adolescent mice; postulation of unique roles of D3receptors and BDNF in place preference acquisition

Andrés Ciudad‐Roberts; Jorge Camarasa; Carlos J. Ciudad; David Pubill; Elena Escubedo

doi:10.1111/bph.13266

journal article Oct 01, 2015

Alcohol enhances the psychostimulant and conditioning effects of mephedrone in adolescent mice; postulation of unique roles of D3receptors and BDNF in place preference acquisition

Andrés Ciudad‐Roberts Jorge Camarasa Carlos J. Ciudad David Pubill Elena Escubedo

British Journal of Pharmacology Vol. 172 No. 20 pp. 4970-4984 · Wiley

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Abstract

Background and PurposeThe psychostimulant mephedrone is often consumed in combination with alcohol (EtOH). This kind of drug consumption during adolescence is a matter of concern.Experimental ApproachWe studied, in adolescent CD‐1 mice, whether EtOH could enhance the psychostimulant (locomotor acivity) and rewarding [conditioned place preference (CPP)] effects of mephedrone. We also determined the transcriptional changes associated with a conditioning treatment with these drugs.Key ResultsMephedrone (10 mg·kg−1) increased locomotor activity, which was further enhanced by 40% when combined with EtOH (1 g·kg−1). This enhancement was blocked by haloperidol. Furthermore, mephedrone (25 mg·kg−1) induced CPP, which increased by 70% when administered with a dose of EtOH that was not conditioning by itself (0.75 g·kg−1). There was enhanced expression of the D3dopamine receptor mRNA (Drd3) andArpc5in all drug‐treated groups. The D3receptor antagonist SB‐277011A and the BDNF receptor antagonist ANA‐12 completely prevented CPP as well as the increases inDrd3in all groups. Accordingly, increased expression of BDNF mRNA in medial prefrontal cortex was detected at 2 and 4 h after mephedrone administration.Conclusions and ImplicationsIf translated to humans, the enhancement of mephedrone effects by ethanol could result in increased abuse liability. D3receptors and BDNF play a key role in the establishment of CPP by mephedrone, although an accompanying increase in other synaptic plasticity‐related genes may also be necessary.

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Details

Published: Oct 01, 2015
Vol/Issue: 172(20)
Pages: 4970-4984
License: View

Authors

A

Andrés Ciudad‐Roberts

Department of Pharmacology and Therapeutic Chemistry (Pharmacology Section), Institute of Biomedicine (IBUB), Faculty of Pharmacy Universitat de Barcelona Barcelona Spain

J

Jorge Camarasa

Department of Pharmacology and Therapeutic Chemistry (Pharmacology Section), Institute of Biomedicine (IBUB), Faculty of Pharmacy Universitat de Barcelona Barcelona Spain

C

Carlos J. Ciudad

Department of Biochemistry and Molecular Biology, Institute of Biomedicine (IBUB), Faculty of Pharmacy Universitat de Barcelona Barcelona Spain

D

David Pubill

Department of Pharmacology and Therapeutic Chemistry (Pharmacology Section), Institute of Biomedicine (IBUB), Faculty of Pharmacy Universitat de Barcelona Barcelona Spain

E

Elena Escubedo

Department of Pharmacology and Therapeutic Chemistry (Pharmacology Section), Institute of Biomedicine (IBUB), Faculty of Pharmacy Universitat de Barcelona Barcelona Spain

Funding

Generalitat de Catalunya Award: 2009SGR977

Cite This Article

Andrés Ciudad‐Roberts, Jorge Camarasa, Carlos J. Ciudad, et al. (2015). Alcohol enhances the psychostimulant and conditioning effects of mephedrone in adolescent mice; postulation of unique roles of D3receptors and BDNF in place preference acquisition. British Journal of Pharmacology, 172(20), 4970-4984. https://doi.org/10.1111/bph.13266

Alcohol enhances the psychostimulant and conditioning effects of mephedrone in adolescent mice; postulation of unique roles of D3receptors and BDNF in place preference acquisition

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