Mephedrone, compared with MDMA (ecstasy) and amphetamine, rapidly increases both dopamine and 5-HT levels in nucleus accumbens of awake rats

The designer drug mephedrone, compared with MDMA (ecstasy) and amphetamine in rats, rapidly increased dopamine levels in the nucleus accumbens by 496% and serotonin levels by 941%, closely matching MDMA's serotonin release but also producing an amphetamine-like fast dopamine surge and elimination. Amphetamine raised dopamine by 412% and serotonin by only 165%. Mephedrone's dopamine levels cleared within 25 minutes, versus 303 minutes for MDMA, suggesting its brief but potent effect on the brain's reward system may underlie strong addictive potential. Locomotor activity increased most with amphetamine; mephedrone and MDMA had weaker, shorter effects.

Study at a glance

Abstract

BACKGROUND AND PURPOSE: The designer drug 1-(4-methylphenyl)-2-methylaminopropan-1-one (4-methylmethcathinone, mephedrone) is reported to possess psychostimulant, entactogenic and hallucinogenic effects. The purpose of this study was to examine the effects of acute administration of mephedrone on extracellular levels of dopamine (DA) and 5-HT in the nucleus accumbens of awake rats and compare these effects with those induced by 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) and amphetamine. EXPERIMENTAL APPROACH: Microdialysis sampling was performed while simultaneously recording locomotor activity in rats and the monoamines were determined by HPLC with electrochemical detection. KEY RESULTS: Mephedrone (3 mg·kg(−1) s.c.) and (+)-amphetamine (1 mg·kg(−1) s.c.) caused rapid increases in extracellular DA levels of 496% and 412%, respectively, whereas MDMA (3 mg·kg(−1) s.c.) showed only a moderate effect (235%). The corresponding 5-HT levels increased to 941% (mephedrone) and 911% (MDMA), but only to 165% following amphetamine. The calculated t(1/2) values for elimination rate of mephedrone, MDMA and amphetamine-induced increases in extracellular DA levels were 25, 303 and 51 min, the corresponding t(1/2) values for 5-HT were 26, 48 and 84 min, respectively. Locomotor activity was increased most by amphetamine, whereas both mephedrone and MDMA showed about three times lower and shorter-lasting effects. CONCLUSIONS AND IMPLICATIONS: The neurochemical and functional properties of mephedrone resemble those of MDMA, but it also shows an amphetamine-like effect in that it evokes a rapid release and elimination of DA in the brain reward system, a feature that may contribute to its potent re-inforcing properties.