Dopaminergic activity in depressed smokers: a positron emission tomography study

Synapse. 2009 Aug;63(8):681-9. doi: 10.1002/syn.20646.


Tobacco dependence is highly prevalent in depressed patients. We assessed changes in [(11)C]-raclopride binding potential (BP) using positron emission tomography (PET) before and after the oral administration of d-amphetamine in healthy controls and unmedicated patients with current depression with and without current tobacco dependence. Over a single study day 2 [(11)C]-raclopride positron emission tomography scans were taken in 38 subjects: at baseline and 2 h following oral d-amphetamine 30 mg. Twenty controls (9 smokers, 11 nonsmokers) and 18 subjects with current major depressive episode (8 smokers, 10 non-smokers). Striatal [(11)C]-raclopride binding potential was measured before and after d-amphetamine administration. Depressed smokers had a lower baseline [(11)C]-raclopride binding potential compared with both control non-smokers (P < 0.007) and depressed non-smokers (P < 0.001). There was a main effect of smoking status on amphetamine-induced change in [(11)C]-raclopride binding potential (P < 0.02), but no main effect of depression. This may be due to a floor effect because of the low BP at baseline. Depressed subjects reported significant increase of positive mood after d-amphetamine administration compared with controls (depressed smokers vs. control smokers: P < 0.05; depressed non-smokers vs. controls: P < 0.055). Tobacco dependence appears to decrease d-amphetamine-induced changes in [(11)C]-raclopride binding potential as measured by positron emission tomography. Comorbid major depression and tobacco dependence exacerbates this effect, suggesting an altered dopamine system in comorbid patients.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Amphetamine / pharmacology
  • Binding, Competitive / drug effects
  • Depression / diagnostic imaging*
  • Depression / etiology*
  • Dopamine / metabolism*
  • Dopamine Antagonists / metabolism
  • Dopamine Uptake Inhibitors / pharmacology
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Male
  • Middle Aged
  • Pain Measurement
  • Positron-Emission Tomography*
  • Raclopride / metabolism
  • Single-Blind Method
  • Statistics as Topic
  • Tobacco Use Disorder / complications*
  • Young Adult


  • Dopamine Antagonists
  • Dopamine Uptake Inhibitors
  • Raclopride
  • Amphetamine
  • Dopamine