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

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 [¹¹C]-(+)-PHNO, which binds to D_2/3 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.