Effects of D1 and D2 receptor antagonists on the discriminative stimulus effects of methylendioxypyrovalerone and mephedrone in male Sprague-Dawley rats trained to discriminate D-amphetamine

Abstract

Psychopharmacology research has amassed substantial evidence for similarities between synthetic cathinones and other commonly abused psychostimulants. Few studies have utilized drug discrimination methods to investigate synthetic cathinones, and the precise neurochemical substrates underlying their interoceptive effects have not been examined. The present study assessed the involvement of D1 and D2 dopaminergic receptors in the stimulus effects of 3,4-methylenedioxypyrovalerone (MDPV) and mephedrone (MEPH) in rats trained to discriminate D-amphetamine. Eight male Sprague-Dawley rats were trained to discriminate 0.5 mg/kg D-amphetamine (AMPH) from saline. Dose-response curves were then generated with AMPH (0.0-1.0 mg/kg), MDPV (0.0-1.0 mg/kg), and MEPH (0.0-2.0 mg/kg). Subsequently, Sch 39166 (0.3 mg/kg) and haloperidol (0.5 mg/kg) were administered in combination with select doses of MDPV and MEPH. Both MDPV and MEPH produced full substitution for AMPH. Sch 39166 produced a downward shift in the MDPV and MEPH dose-response curves and haloperidol produced similar results with MDPV. These preliminary findings indicate that MDPV and MEPH produce interoceptive stimuli that are similar to those produced by AMPH and that D1 and D2 dopamine receptors contribute to these effects. Additional studies are warranted to investigate the contribution of other receptor mechanisms involved in the interoceptive stimuli produced by synthetic cathinones.

Figure 1

Dose-response curves determined from stimulus generalization tests with AMPH, MDPV, and MEPH and stimulus antagonism tests with 0.3 mg/kg Sch 39166 or 0.5 mg/kg haloperidol in combination with selected doses of MDPV or MEPH in rats trained to discriminate 0.5 mg/kg AMPH from saline (n=8). Graphs in the upper panel depict percentage of responses on the AMPH-appropriate lever. Graphs in the lower panel depict response rate. Individual points represent group means (± SEM). Significant Dunnett's multiple comparison tests on response rate between selected doses and vehicle are represented by * (p < .05) or ** (p < .01).