Imaging the D3 dopamine receptor across behavioral and drug addictions: Positron emission tomography studies with [(11)C]-(+)-PHNO

Eur Neuropsychopharmacol. 2015 Sep;25(9):1410-20. doi: 10.1016/j.euroneuro.2015.06.002. Epub 2015 Jun 20.


Chronic drug use has been associated with dopaminergic abnormalities, detectable in humans with positron emission tomography (PET). Among these, a hallmark feature is low D2 dopamine receptor availability, which has been linked to clinical outcomes, but has not yet translated into a therapeutic strategy. The D3 dopamine receptor on the other hand has gained increasing attention, as, in contrast to D2, chronic exposure to drugs has been shown to up-regulate this receptor subtype in preclinical models of addiction-a phenomenon linked to dopamine system sensitization and drug-seeking. The present article summarizes the literature to date in humans, suggesting that the D3 receptor may indeed contribute to core features of addiction such as impulsiveness and cognitive impairment. A particularly useful tool in investigating this question is the PET imaging probe [(11)C]-(+)-PHNO, which binds to D2/3 dopamine receptors but has preferential affinity for D3. This technique has been used to demonstrate D3 up-regulation in humans, and can be applied to assess pharmacological interventions for development of D3-targeted strategies in addiction treatment.

Keywords: Addiction; D(3) dopamine receptor; Impulsiveness; Positron emission tomography; [(11)C]-(+)-PHNO.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / diagnostic imaging*
  • Brain / metabolism*
  • Humans
  • Oxazines
  • Positron-Emission Tomography / methods
  • Radiopharmaceuticals
  • Receptors, Dopamine D3 / metabolism*
  • Substance-Related Disorders / diagnostic imaging*
  • Substance-Related Disorders / metabolism*
  • Substance-Related Disorders / psychology


  • Oxazines
  • Radiopharmaceuticals
  • Receptors, Dopamine D3
  • naxagolide