Mephedrone, compared with MDMA (ecstasy) and amphetamine, rapidly increases both dopamine and 5-HT levels in nucleus accumbens of awake rats
British Journal of Pharmacology – May 26, 2011
Source: OpenAlex
Summary
Mephedrone dramatically boosts dopamine levels, increasing them by 496% in the nucleus accumbens of awake rats, surpassing MDMA's 235% and amphetamine's 412%. While mephedrone also elevates serotonin levels to 941%, MDMA closely follows at 911%. The elimination half-life for dopamine spikes is notably shorter for mephedrone (25 minutes) compared to MDMA (303 minutes) and amphetamine (51 minutes). Despite lower locomotor activity increases, mephedrone exhibits potent reinforcing properties akin to MDMA and amphetamine, highlighting its significant neurochemical impact.
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.