Combined effects of mephedrone and cocaine on locomotor activity and conditioned place preference in male Sprague-Dawley rats.

Abstract

Mephedrone (MEPH) is one of several synthetic cathinone derivatives and a common constituent of illicit 'bath salts'. Concomitant use of MEPH with other psychostimulants is common among recreational users, but their combined effects have not been evaluated rigorously. In experiment 1, 56 male Sprague-Dawley rats were administered saline, MEPH (1 or 5 mg/kg), COC (5 mg/kg), or a mixture of MEPH (1 or 5 mg/kg) + COC (5 mg/kg) for seven consecutive days. Following a 10-day drug washout, rats were given a challenge injection of COC (5 mg/kg). Locomotor activity was recorded for 60 minutes immediately before and for 60 minutes immediately after injections on days 1, 7, and 17. In experiment 2, an unbiased conditioned place preference procedure was implemented over a 10-day period with a separate group of 66 male Sprague-Dawley rats randomly assigned to similar drug treatments used in experiment. Results of experiment 1 indicated significant increases in horizontal activity after repeated treatment with MEPH+COC mixtures, but not with either drug alone. Additionally, rats pretreated with MEPH + COC mixtures exhibited an augmented response to cocaine following drug abstinence. Evidence for CPP was established in rats treated with 5 mg/kg MEPH, 5 mg/kg COC and the 5 mg/kg MEPH + 5 mg/kg COC mixture. In conclusion, cocaine and mephedrone may have additive locomotor stimulant effects, although further assessment with a wider range of dose combinations must be evaluated. As a precautionary note, concurrent use of these substances may pose an enhanced risk for abuse.