title: Imaging dopamine transmission in cocaine dependence: link between neurochemistry and response to treatment.
abstract: OBJECTIVE
  Previous research has shown that dopamine signaling in the limbic striatum is crucial for selecting adaptive, motivated behavior and that disrupted dopamine transmission is associated with impulsive and maladaptive behavior. In humans, positron emission tomography (PET) imaging studies have shown that cocaine dependence is associated with the dysregulation of striatal dopamine signaling, which is linked to cocaine-seeking behavior. The goal of the present study was to investigate whether this association applies to the treatment setting. The authors hypothesized that dopamine signaling in the limbic striatum would be associated with response to a behavioral treatment that uses positive reinforcement to replace impulsive cocaine use with constructive personal goals.
  
  
  METHODS
  Prior to treatment, cocaine-dependent subjects underwent two PET scans using [(11)C]raclopride, before and after the administration of a stimulant (methylphenidate), for measurement of striatal dopamine D(2/3) receptor binding and presynaptic dopamine release.
  
  
  RESULTS
  Both of the outcome measures were lower in the volunteers who did not respond to treatment than in those who experienced a positive treatment response.
  
  
  CONCLUSIONS
  These findings provide insight into the neurochemistry of treatment response and show that low dopamine transmission is associated with treatment failure. In addition, these data suggest that the combination of behavioral treatment with methods that increase striatal dopamine signaling might serve as a therapeutic strategy for cocaine dependence.
authors.affiliation: Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, USA. dm437@columbia.edu
authors.forename: Diana
authors.initials: D
authors.lastname: Martinez
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Carpenter
authors.forename: Fei
authors.initials: F
authors.lastname: Liu
authors.forename: Mark
authors.initials: M
authors.lastname: Slifstein
authors.forename: Allegra
authors.initials: A
authors.lastname: Broft
authors.forename: Alessandra Calvo
authors.initials: AC
authors.lastname: Friedman
authors.forename: Dileep
authors.initials: D
authors.lastname: Kumar
authors.forename: Ronald
authors.initials: R
authors.lastname: Van Heertum
authors.forename: Herbert D
authors.initials: HD
authors.lastname: Kleber
authors.forename: Edward
authors.initials: E
authors.lastname: Nunes
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D000697:Central Nervous System Stimulants / Q000627:therapeutic use; D019970:Cocaine-Related Disorders / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism*; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008774:Methylphenidate / Q000627:therapeutic use; D009448:Neurochemistry; D049268:Positron-Emission Tomography; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D000697:Central Nervous System Stimulants; D017448:Receptors, Dopamine D2; D008774:Methylphenidate; D004298:Dopamine