Alcohol enhances the psychostimulant and conditioning effects of mephedrone in adolescent mice; postulation of unique roles of D3 receptors and BDNF in place preference acquisition.

BACKGROUND AND
PURPOSE: The psychostimulant mephedrone is often consumed in combination with alcohol (EtOH). This kind of drug consumption during adolescence is a matter of concern. EXPERIMENTAL APPROACH: We 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
RESULTS: Mephedrone (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 D3 dopamine receptor mRNA (Drd3) and Arpc5 in all drug-treated groups. The D3 receptor antagonist SB-277011A and the BDNF receptor antagonist ANA-12 completely prevented CPP as well as the increases in Drd3 in all groups. Accordingly, increased expression of BDNF mRNA in medial prefrontal cortex was detected at 2 and 4 h after mephedrone administration. CONCLUSIONS AND IMPLICATIONS: If translated to humans, the enhancement of mephedrone effects by ethanol could result in increased abuse liability. D3 receptors 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.