title: The D2/3 dopamine receptor in pathological gambling: a positron emission tomography study with [11C]-(+)-propyl-hexahydro-naphtho-oxazin and [11C]raclopride.
abstract: OBJECTIVE
  Pathological gambling (PG) shares diagnostic features with substance use disorder (SUD), but the neurochemical mechanisms underlying PG are poorly understood. Because dopamine (DA), a neurotransmitter implicated in reward and reinforcement, is probably involved, we used positron emission tomography (PET) to test whether PG is associated with abnormalities in D2 and D3 receptor levels, as observed in SUD.
  
  
  METHODS
  Case-control study comparing PG to healthy control (HC) subjects.
  
  
  METHODS
  Academic research imaging centre.
  
  
  METHODS
  Thirteen non-treatment-seeking males meeting DSM-IV criteria for PG, and 12 matched HC (11 of whom completed PET).
  
  
  METHODS
  Two PET scans (one with the D3 receptor preferring agonist [11C]-(+)-propyl-hexahydro-naphtho-oxazin (PHNO) and the other with [11C]raclopride) to assess D(2/3) DA receptor availability, and behavioural measures (self-report questionnaires and slot-machine game) to assess subjective effects and relationships to PET measures.
  
  
  RESULTS
  Binding of both radiotracers did not differ between groups in striatum or substantia nigra (SN) (all P > 0.1). Across PG, [11C]-(+)-PHNO binding in SN, where the signal is attributable primarily to D3 receptors, correlated with gambling severity (r = 0.57, P = 0.04) and impulsiveness (r = 0.65, P = 0.03). In HC, [11C]raclopride binding in dorsal striatum correlated inversely with subjective effects of gambling (r = -0.70, P = 0.03) and impulsiveness (r = -0.70, P = 0.03).
  
  
  CONCLUSIONS
  Unlike with substance use disorder, there appear to be no marked differences in D2 /D3 levels between healthy subjects and pathological gamblers, suggesting that low receptor availability may not be a necessary feature of addiction. However, relationships between [11C]-(+)-PHNO binding and gambling severity/impulsiveness suggests involvement of the D3 receptor in impulsive/compulsive behaviours.
authors.affiliation: Addiction Imaging Research Group, Centre for Addiction and Mental Health, Toronto, ON, Canada. isabelle_boileau@camh.net
authors.forename: Isabelle
authors.initials: I
authors.lastname: Boileau
authors.forename: Doris
authors.initials: D
authors.lastname: Payer
authors.forename: Bindiya
authors.initials: B
authors.lastname: Chugani
authors.forename: Daniela
authors.initials: D
authors.lastname: Lobo
authors.forename: Arian
authors.initials: A
authors.lastname: Behzadi
authors.forename: Pablo M
authors.initials: PM
authors.lastname: Rusjan
authors.forename: Sylvain
authors.initials: S
authors.lastname: Houle
authors.forename: Alan A
authors.initials: AA
authors.lastname: Wilson
authors.forename: Jerry
authors.initials: J
authors.lastname: Warsh
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Kish
authors.forename: Martin
authors.initials: M
authors.lastname: Zack
mesh_terms: D000328:Adult; D016739:Behavior, Addictive / Q000378:metabolism*; D001921:Brain / Q000000981:diagnostic imaging*; D002250:Carbon Radioisotopes; D016022:Case-Control Studies; D018492:Dopamine Antagonists; D005715:Gambling / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010078:Oxazines; D049268:Positron-Emission Tomography / Q000379:methods*; D020891:Raclopride; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050637:Receptors, Dopamine D3 / Q000378:metabolism; D057566:Self Report; D055815:Young Adult
chemical_list: D002250:Carbon Radioisotopes; D018492:Dopamine Antagonists; D010078:Oxazines; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D020891:Raclopride