What is the role of the D3 receptor in addiction? A mini review of PET studies with [11C]-(+)-PHNO

• D3 dopamine receptors are distributed on key neurocircuitry underlying addiction.
• D3 receptors are upregulated in animal models of addiction.
• [11C]-(+)-PHNO is a novel PET probe to investigate D3 receptors in living humans.
• PET evidence shows that D3 receptor levels are increased in human addiction.
• There is translational potential in D3 antagonism with [11C]-(+)-PHNO PET as guide.

The chronic use of drugs, including psychostimulants such as cocaine and amphetamine, has been associated with low D2/3 dopamine receptor availability, which in turn has been linked to poor clinical outcome. In contrast, recent studies focused on the D3 receptor (a member of the D2-like receptor family) suggest that chronic exposure to stimulant drugs can up-regulate this receptor subtype, which, in preclinical models, is linked to dopamine system sensitization — a process hypothesized to contribute to relapse in addiction. In this mini review we present recent human data suggesting that the D3 receptor may contribute to core features of addiction, and discuss the usefulness of the PET imaging probe [11C]-(+)-PHNO in investigating this question.