Role of 6-monoacetylmorphine in the acute release of striatal dopamine induced by intravenous heroin

Int J Neuropsychopharmacol. 2014 Sep;17(9):1357-65. doi: 10.1017/S1461145714000169. Epub 2014 Feb 27.


After injection, heroin is rapidly metabolized to 6-monoacetylmorphine (6-MAM) and further to morphine. As morphine has been shown to increase striatal dopamine, whereas 6-MAM has not been studied in this respect, we gave i.v. injections of 3 μmol 6-MAM, morphine or heroin to rats. Opioids were measured in blood, and dopamine and opioids in microdialysate from brain striatal extracellular fluid (ECF), by UPLC-MS/MS. After 6-MAM injection, 6-MAM ECF concentrations increased rapidly, and reached Cmax of 4.4 μM after 8 min. After heroin injection, 6-MAM increased rapidly in blood and reached Cmax of 6.4 μM in ECF after 8 min, while ECF Cmax for heroin was 1.2 μM after 2 min. T max for morphine in ECF was 29 and 24 min following 6-MAM and heroin administration, respectively, with corresponding Cmax levels of 1 and 2 μM. Dopamine levels peaked after 8 and 14 min following 6-MAM and heroin administration, respectively. The dopamine responses were equal, indicating no dopamine release by heroin per se. Furthermore, 6-MAM, and not morphine, appeared to mediate the early dopamine response, whereas morphine administration, giving rise to morphine ECF concentrations similar to those observed shortly after 6-MAM injection, did not increase ECF dopamine. 6-MAM appeared accordingly to be the substance responsible for the early increase in dopamine observed after heroin injection. As 6-MAM was formed rapidly from heroin in blood, and was the major substance reaching the brain after heroin administration, this also indicates that factors influencing blood 6-MAM concentrations might change the behavioural effects of heroin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics, Opioid / administration & dosage*
  • Animals
  • Area Under Curve
  • Corpus Striatum / drug effects*
  • Corpus Striatum / metabolism*
  • Dopamine / metabolism*
  • Extracellular Fluid / drug effects
  • Extracellular Fluid / metabolism
  • Heroin / administration & dosage*
  • Heroin / metabolism
  • Injections, Intravenous
  • Male
  • Microdialysis
  • Morphine / pharmacology
  • Morphine Derivatives / administration & dosage
  • Morphine Derivatives / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors
  • Wakefulness / drug effects


  • Analgesics, Opioid
  • Morphine Derivatives
  • Heroin
  • Morphine
  • 6-O-monoacetylmorphine
  • Dopamine