Alcohol potentiates the psychostimulant and reinforcing effects of mephedrone in adolescent mice: role of D3 receptors and associated changes in gene expression

Mephedrone (Meph) is a novel psychostimulant whose recreational consumption is often associated to other drugs, especially alcohol (EtOH). This kind of drug consumption during adolescence is a matter of concern. We studied, in adolescent CD-1 mice, whether low-moderate doses of EtOH could enhance the psychostimulant (locomotor acivity) and reinforcing (conditioned place preference, CPP) effects of mephedrone. Simultaneously we also determined the most relevant transcriptional changes associated to a reinforcing treatment. A single dose of Meph (10 mg/kg, sc) induced an increase of about 100% in locomotor activity, which was a further enhanced by 40% when associated with a dose of EtOH (1 g/kg). The hyperlocomotion was partially antagonized by ketanserin and haloperidol, but only haloperidol blocked the potentiation induced by EtOH. Furthermore, Meph (25 mg/kg) induced significant positive conditioning, which increased by 70% when administered with 0.75 mg/kg EtOH. Microarray analysis of mRNA extracted from anterior striata of the mice used in CPP experiments reported significant modifications in genes related with neurotransmission and synaptic plasticity, which were further validated by Real-time PCR for all three drug-treated groups.

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