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

Br J Pharmacol. 2011 Dec;164(8):1949-58. doi: 10.1111/j.1476-5381.2011.01499.x.


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 reinforcing properties.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3,4-Dihydroxyphenylacetic Acid / metabolism
  • Amphetamine / pharmacology*
  • Animals
  • Chromatography, High Pressure Liquid
  • Dopamine / metabolism*
  • Hydroxyindoleacetic Acid / metabolism
  • Locomotion / drug effects
  • Male
  • Methamphetamine / analogs & derivatives*
  • Methamphetamine / pharmacology
  • N-Methyl-3,4-methylenedioxyamphetamine / pharmacology*
  • Nucleus Accumbens / drug effects*
  • Nucleus Accumbens / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Serotonin / metabolism*


  • 3,4-Dihydroxyphenylacetic Acid
  • Serotonin
  • Methamphetamine
  • Hydroxyindoleacetic Acid
  • mephedrone
  • Amphetamine
  • N-Methyl-3,4-methylenedioxyamphetamine
  • Dopamine