title: Imaging of dopamine D2/3 agonist binding in cocaine dependence: a [11C]NPA positron emission tomography study.
abstract: OBJECTIVE
  Positron emission tomography (PET) studies performed with [(11) C]raclopride have consistently reported lower binding to D(2/3) receptors and lower amphetamine-induced dopamine (DA) release in cocaine abusers relative to healthy controls. A limitation of these studies that were performed with D(2/3) antagonist radiotracers such as [(11) C]raclopride is the failure to provide information that is specific to D(2/3) receptors configured in a state of high affinity for the agonists (i.e., D(2/3) receptors coupled to G-proteins, D(2/3 HIGH) ). As the endogenous agonist DA binds with preference to D(2/3 HIGH) relative to D(2/3 LOW) receptors (i.e., D(2/3) receptors uncoupled to G-proteins) it is critical to understand the in vivo status of D(2/3 HIGH) receptors in cocaine dependence. Thus, we measured the available fraction of D(2/3) (HIGH) receptors in 10 recently abstinent cocaine abusers (CD) and matched healthy controls (HC) with the D(2/3) antagonist and agonist PET radiotracers [(11) C]raclopride and [(11) C]NPA.
  
  
  METHODS
  [(11) C]raclopride and [(11) C]NPA binding potential (BP) (BP(ND) ) in the striatum were measured with kinetic analysis using the arterial input function. The available fraction of D(2/3 HIGH) receptors, i.e., % R(HIGH) available = D(2/3 HIGH) /(D(2/3 HIGH) + D(2/3 LOW) ) was then computed as the ratio of [(11) C]NPA BP(ND) /[(11) C]raclopride BP(ND) .
  
  
  RESULTS
  No differences in striatal [(11) C]NPA BP(ND) (HC = 1.00 ± 0.17; CD = 0.97 ± 0.17, P = 0.67) or available % R(HIGH) (HC = 39% ± 5%; CD = 41% ± 5%, P = 0.50) was observed between cocaine abusers and matched controls.
  
  
  CONCLUSIONS
  The results of this [(11) C]NPA PET study do not support alterations in D(2/3 HIGH) binding in the striatum in cocaine dependence.
authors.affiliation: Department of Radiology, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA. narendranr@upmc.edu
authors.forename: Rajesh
authors.initials: R
authors.lastname: Narendran
authors.forename: Diana
authors.initials: D
authors.lastname: Martinez
authors.forename: Neale Scott
authors.initials: NS
authors.lastname: Mason
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Lopresti
authors.forename: Michael L
authors.initials: ML
authors.lastname: Himes
authors.forename: Chi-Min
authors.initials: CM
authors.lastname: Chen
authors.forename: Maureen A
authors.initials: MA
authors.lastname: May
authors.forename: Julie C
authors.initials: JC
authors.lastname: Price
authors.forename: Chester A
authors.initials: CA
authors.lastname: Mathis
authors.forename: W Gordon
authors.initials: WG
authors.lastname: Frankle
mesh_terms: D000293:Adolescent; D000328:Adult; D001058:Apomorphine / Q000031:analogs & derivatives / Q000378:metabolism / Q000493:pharmacokinetics; D019970:Cocaine-Related Disorders / Q000000981:diagnostic imaging / Q000378:metabolism*; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism*; D018491:Dopamine Agonists / Q000378:metabolism* / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods*; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000378:metabolism*; D050637:Receptors, Dopamine D3 / Q000819:agonists / Q000378:metabolism*; D055815:Young Adult
chemical_list: D018491:Dopamine Agonists; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; C009074:N-n-propylnorapomorphine; D001058:Apomorphine