Differential effects of 3,4-methylenedioxypyrovalerone (MDPV) and 4-methylmethcathinone (mephedrone) in rats trained to discriminate MDMA or a d-amphetamine + MDMA mixture

Abstract

Rationale: Recent reports on the abuse of novel synthetic cathinone derivatives call attention to serious public health risks of these substances. In response to this concern, a growing body of preclinical research has characterized the psychopharmacology of these substances, particularly mephedrone (MEPH) or methylenedioxypyrovalerone (MDPV), noting their similarities to 3,4-methylenedioxymethamphetamine (MDMA) and cocaine. Few studies have utilized drug discrimination methodology to characterize the psychopharmacological properties of these substances.

Objectives: The present study employed a rodent drug discrimination assay to further characterize the stimulus effects of MEPH and MDPV in comparison to MDMA and to a drug mixture comprised of d-amphetamine and MDMA.

Methods: Eight male Sprague-Dawley rats were trained to discriminate 1.5 mg/kg MDMA, and eight rats were trained to discriminate a mixture of 1.5 mg/kg MDMA and 0.5 mg/kg d-amphetamine (MDMA + AMPH) from vehicle. Substitution tests were conducted with MDMA, d-amphetamine, MDPV, MEPH, and cocaine.

Results: Dose-response curves generated with MDMA and MEPH were comparable between training groups. In contrast, AMPH, MDPV, and cocaine produced only partial substitution in animals trained to discriminate MDMA but produced full substitution in animals trained to discriminate the MDMA + AMPH mixture.

Conclusions: These findings indicate that MDPV's effects may be more similar to those of traditional psychostimulants, whereas MEPH exerts stimulus effects more similar to those of MDMA. Additional experiments with selective DA and 5-hydroxytryptamine (5-HT) receptor antagonists are required to further elucidate specific receptor mechanisms mediating the discriminative stimulus effects of MDPV and mephedrone.

Keywords: Cocaine; Drug discrimination; MDPV; Mephedrone; Rats; d-Amphetamine.

Fig. 1

Dose response curves determined from stimulus generalization tests with MDMA, mephedrone, MDPV, cocaine, and d-amphetamine in rats trained to discriminate a 1.5 mg/kg MDMA (n = 7) or a mixture of 1.5 mg/kg MDMA + 0.5 mg/kg d-amphetamine (n = 8) from saline. Graphs in the upper panel depict percentage of responses on the drug-appropriate lever. Graphs in the lower panel depict response rate. Individual points represent group means (± S.E. M.). MDMA+AMPH mixture group (■) and MDMA alone group (○). For response rate, significant Bonferroni multiple comparison tests between selected doses and saline are represented by * (p < 0.05).