PET imaging of dopamine transporter and drug craving during methadone maintenance treatment and after prolonged abstinence in heroin users

Eur J Pharmacol. 2008 Jan 28;579(1-3):160-6. doi: 10.1016/j.ejphar.2007.09.042. Epub 2007 Oct 10.


It has been documented that methadone maintenance treatment is effective in reducing drug craving and relevant risk behaviors in heroin users. However, it is not understood whether methadone maintenance treatment impairs the dopamine transporter in the striatum. To establish whether chronic opiate use might impair brain dopamine neurons in humans, we assessed dopamine transporter (DAT) uptake function in the striatum (caudate and putamen), and analyzed the correlation between DAT in the striatum and heroin craving and subjective anxiety in former heroin users with prolonged abstinence and in patients receiving methadone maintenance treatment. Binding of [(11)C]-2beta-carbomethoxy-3beta-aryltropane ([(11)C] CFT) as a brain dopamine transporter ligand was measured with positron emission tomography (PET) in eleven former heroin users with prolonged abstinence, ten patients receiving methadone maintenance treatment and ten healthy control subjects. Heroin craving and subjective anxiety in prolonged abstinence and methadone maintenance treatment groups were assessed and the correlations between DAT of striatum and heroin craving or subjective anxiety were determined. In comparison with healthy control subjects, methadone maintenance treatment subjects had lower DAT uptake function in the bilateral caudate and putamen and prolonged abstinence subjects showed significantly lower DAT uptake function in the bilateral caudate. Moreover, in comparison to the prolonged abstinence subjects, the methadone maintenance treatment subjects showed significant decreases of DAT uptake in the bilateral putamen. DAT uptake function in bilateral striatum was not associated with heroin craving in prolonged abstinence or in methadone maintenance treatment subjects; however, DAT uptake function in the bilateral caudate was significantly correlated with subjective anxiety in methadone maintenance treatment subjects. Our findings suggest that chronic opioid use induces long-lasting striatum dopamine neuron impairment, and prolonged withdrawal from opioids can benefit the recovery of impaired dopamine neurons in the brain.

Publication types

  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anxiety / etiology
  • Caudate Nucleus / drug effects
  • Caudate Nucleus / metabolism
  • Dopamine / metabolism
  • Dopamine Plasma Membrane Transport Proteins / drug effects*
  • Dopamine Plasma Membrane Transport Proteins / metabolism
  • Female
  • Heroin Dependence / psychology
  • Heroin Dependence / rehabilitation*
  • Humans
  • Male
  • Methadone / adverse effects*
  • Middle Aged
  • Narcotics / adverse effects*
  • Neurons / drug effects
  • Neurons / metabolism
  • Positron-Emission Tomography
  • Putamen / drug effects
  • Putamen / metabolism
  • Substance Withdrawal Syndrome / physiopathology
  • Substance Withdrawal Syndrome / psychology


  • Dopamine Plasma Membrane Transport Proteins
  • Narcotics
  • Methadone
  • Dopamine