title: Cocaine dependence and d2 receptor availability in the functional subdivisions of the striatum: relationship with cocaine-seeking behavior.
abstract: Striatal dopamine D2 receptors have been implicated in the neurobiology of cocaine addiction. Previous imaging studies showed reduced striatal D2 receptor availability in chronic cocaine abusers, and animal studies suggested that low D2 receptor availability promotes cocaine self-administration. Here, D2 receptor availability was assessed with positron emission tomography (PET) and [11C]raclopride in the limbic, associative, and sensori-motor subdivisions of the striatum in 17 recently detoxified chronic cocaine-dependent (CCD) subjects and 17 matched healthy control (HC) subjects. In addition, the relationship between regional D2 receptor availability and behavioral measures obtained in cocaine self-administration sessions was investigated in CCD subjects. [11C]Raclopride binding potential was significantly reduced by 15.2% in the limbic striatum, 15.0% in the associative striatum, and 17.1% in the sensori-motor striatum in CCD subjects compared to HC subjects. In CCD subjects, no relationship was detected between D2 availability in striatal regions and either the positive effects of smoked cocaine or the choice of cocaine over an alternative reinforcer (money) following a priming dose of cocaine (a laboratory model of relapse). Thus, this study confirms previous reports of a modest decrease in D2 receptor availability in CCD subjects, and establishes that this decrease is generalized throughout the striatum. However, this study failed to demonstrate a relationship between D2 receptor availability and cocaine-induced cocaine-taking behavior. Additional research is warranted to unravel potential neurobiological traits that might confer vulnerability to relapse in detoxified CCD subjects.
authors.affiliation: Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY, USA. dm437@columbia.edu
authors.forename: Diana
authors.initials: D
authors.lastname: Martinez
authors.forename: Allegra
authors.initials: A
authors.lastname: Broft
authors.forename: Richard W
authors.initials: RW
authors.lastname: Foltin
authors.forename: Mark
authors.initials: M
authors.lastname: Slifstein
authors.forename: Dah-Ren
authors.initials: DR
authors.lastname: Hwang
authors.forename: Yiyun
authors.initials: Y
authors.lastname: Huang
authors.forename: Audrey
authors.initials: A
authors.lastname: Perez
authors.forename: W Gordon
authors.initials: WG
authors.lastname: Frankle
authors.forename: Thomas
authors.initials: T
authors.lastname: Cooper
authors.forename: Herbert D
authors.initials: HD
authors.lastname: Kleber
authors.forename: Marian W
authors.initials: MW
authors.lastname: Fischman
authors.forename: Marc
authors.initials: M
authors.lastname: Laruelle
authors.forename: W Gordon
authors.initials: WG
authors.lastname: Frankel
mesh_terms: D000328:Adult; D001665:Binding Sites / Q000187:drug effects; D001931:Brain Mapping; D016022:Case-Control Studies; D002755:Choice Behavior / Q000187:drug effects; D003042:Cocaine / Q000008:administration & dosage*; D019970:Cocaine-Related Disorders / Q000378:metabolism*; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000493:pharmacokinetics; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D020891:Raclopride / Q000493:pharmacokinetics; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D012646:Self Administration; D013997:Time Factors; D014055:Tomography, Emission-Computed / Q000379:methods
chemical_list: D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D017448:Receptors, Dopamine D2; D020891:Raclopride; D003042:Cocaine