Mephedrone, compared with MDMA (ecstasy) and amphetamine, rapidly increases both dopamine and 5-HT levels in nucleus accumbens of awake rats
Ján Kehr, Fumio Ichinose, Shimako Yoshitake, Michel Goiny, T Sievertsson, Fred Nyberg, Takashi Yoshitake
British Journal of Pharmacology May 26, 2011 DOI: 10.1111/j.1476-5381.2011.01499.x (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Awake rats |
| Interventions | Mephedrone MDMA amphetamine |
| Dose | 3 mg·kg(−1) s.c. for mephedrone and MDMA, 1 mg·kg(−1) s.c. for amphetamine |
| Topics | MDMA |
| Keywords | Nucleus accumbens Mephedrone Dopamine Dextroamphetamine Methamphetamine Pharmacology Norepinephrine Anesthesia |
| Key findings | Mephedrone combines MDMA-like serotonin release with amphetamine-like rapid dopamine release and elimination in the nucleus accumbens, which may contribute to its reinforcing properties. |
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.