title: Low Dopamine D2/D3 Receptor Availability is Associated with Steep Discounting of Delayed Rewards in Methamphetamine Dependence.
abstract: BACKGROUND
  Individuals with substance use disorders typically exhibit a predilection toward instant gratification with apparent disregard for the future consequences of their actions. Indirect evidence suggests that low dopamine D2-type receptor availability in the striatum contributes to the propensity of these individuals to sacrifice long-term goals for short-term gain; however, this possibility has not been tested directly. We investigated whether striatal D2/D3 receptor availability is negatively correlated with the preference for smaller, more immediate rewards over larger, delayed alternatives among research participants who met DSM-IV criteria for methamphetamine (MA) dependence.
  
  
  METHODS
  Fifty-four adults (n = 27 each: MA-dependent, non-user controls) completed the Kirby Monetary Choice Questionnaire, and underwent positron emission tomography scanning with [(18)F]fallypride.
  
  
  RESULTS
  MA users displayed steeper temporal discounting (p = 0.030) and lower striatal D2/D3 receptor availability (p < 0.0005) than controls. Discount rate was negatively correlated with striatal D2/D3 receptor availability, with the relationship reaching statistical significance in the combined sample (r = -0.291, p = 0.016) and among MA users alone (r = -0.342, p = 0.041), but not among controls alone (r = -0.179, p = 0.185); the slopes did not differ significantly between MA users and controls (p = 0.5).
  
  
  CONCLUSIONS
  These results provide the first direct evidence of a link between deficient D2/D3 receptor availability and steep temporal discounting. This finding fits with reports that low striatal D2/D3 receptor availability is associated with a higher risk of relapse among stimulant users, and may help to explain why some individuals choose to continue using drugs despite knowledge of their eventual negative consequences. Future research directions and therapeutic implications are discussed.
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles (Drs Ballard, Ishibashi, Dean, and London); Department of Molecular and Medical Pharmacology, University of California Los Angeles (Robertson and Dr London); Brain Research Institute, University of California Los Angeles (Dr London); Veterans Affairs Greater Los Angeles Healthcare System, CA (Drs Ballard, Mandelkern, Ishibashi, and London and Robertson); Department of Physics, University of California Irvine, CA (Dr Mandelkern); Department of Psychology, University of Southern California, Los Angeles, CA (Dr Monterosso and Hsu).
authors.forename: Michael E
authors.initials: ME
authors.lastname: Ballard
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles (Drs Ballard, Ishibashi, Dean, and London); Department of Molecular and Medical Pharmacology, University of California Los Angeles (Robertson and Dr London); Brain Research Institute, University of California Los Angeles (Dr London); Veterans Affairs Greater Los Angeles Healthcare System, CA (Drs Ballard, Mandelkern, Ishibashi, and London and Robertson); Department of Physics, University of California Irvine, CA (Dr Mandelkern); Department of Psychology, University of Southern California, Los Angeles, CA (Dr Monterosso and Hsu).
authors.forename: Mark A
authors.initials: MA
authors.lastname: Mandelkern
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles (Drs Ballard, Ishibashi, Dean, and London); Department of Molecular and Medical Pharmacology, University of California Los Angeles (Robertson and Dr London); Brain Research Institute, University of California Los Angeles (Dr London); Veterans Affairs Greater Los Angeles Healthcare System, CA (Drs Ballard, Mandelkern, Ishibashi, and London and Robertson); Department of Physics, University of California Irvine, CA (Dr Mandelkern); Department of Psychology, University of Southern California, Los Angeles, CA (Dr Monterosso and Hsu).
authors.forename: John R
authors.initials: JR
authors.lastname: Monterosso
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles (Drs Ballard, Ishibashi, Dean, and London); Department of Molecular and Medical Pharmacology, University of California Los Angeles (Robertson and Dr London); Brain Research Institute, University of California Los Angeles (Dr London); Veterans Affairs Greater Los Angeles Healthcare System, CA (Drs Ballard, Mandelkern, Ishibashi, and London and Robertson); Department of Physics, University of California Irvine, CA (Dr Mandelkern); Department of Psychology, University of Southern California, Los Angeles, CA (Dr Monterosso and Hsu).
authors.forename: Eustace
authors.initials: E
authors.lastname: Hsu
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles (Drs Ballard, Ishibashi, Dean, and London); Department of Molecular and Medical Pharmacology, University of California Los Angeles (Robertson and Dr London); Brain Research Institute, University of California Los Angeles (Dr London); Veterans Affairs Greater Los Angeles Healthcare System, CA (Drs Ballard, Mandelkern, Ishibashi, and London and Robertson); Department of Physics, University of California Irvine, CA (Dr Mandelkern); Department of Psychology, University of Southern California, Los Angeles, CA (Dr Monterosso and Hsu).
authors.forename: Chelsea L
authors.initials: CL
authors.lastname: Robertson
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles (Drs Ballard, Ishibashi, Dean, and London); Department of Molecular and Medical Pharmacology, University of California Los Angeles (Robertson and Dr London); Brain Research Institute, University of California Los Angeles (Dr London); Veterans Affairs Greater Los Angeles Healthcare System, CA (Drs Ballard, Mandelkern, Ishibashi, and London and Robertson); Department of Physics, University of California Irvine, CA (Dr Mandelkern); Department of Psychology, University of Southern California, Los Angeles, CA (Dr Monterosso and Hsu).
authors.forename: Kenji
authors.initials: K
authors.lastname: Ishibashi
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles (Drs Ballard, Ishibashi, Dean, and London); Department of Molecular and Medical Pharmacology, University of California Los Angeles (Robertson and Dr London); Brain Research Institute, University of California Los Angeles (Dr London); Veterans Affairs Greater Los Angeles Healthcare System, CA (Drs Ballard, Mandelkern, Ishibashi, and London and Robertson); Department of Physics, University of California Irvine, CA (Dr Mandelkern); Department of Psychology, University of Southern California, Los Angeles, CA (Dr Monterosso and Hsu).
authors.forename: Andy C
authors.initials: AC
authors.lastname: Dean
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles (Drs Ballard, Ishibashi, Dean, and London); Department of Molecular and Medical Pharmacology, University of California Los Angeles (Robertson and Dr London); Brain Research Institute, University of California Los Angeles (Dr London); Veterans Affairs Greater Los Angeles Healthcare System, CA (Drs Ballard, Mandelkern, Ishibashi, and London and Robertson); Department of Physics, University of California Irvine, CA (Dr Mandelkern); Department of Psychology, University of Southern California, Los Angeles, CA (Dr Monterosso and Hsu). elondon@mednet.ucla.edu.
authors.forename: Edythe D
authors.initials: ED
authors.lastname: London
mesh_terms: D000328:Adult; D019969:Amphetamine-Related Disorders / Q000000981:diagnostic imaging / Q000378:metabolism*; D001549:Benzamides / Q000008:administration & dosage; D000697:Central Nervous System Stimulants / Q000633:toxicity; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism*; D039721:Diagnostic and Statistical Manual of Mental Disorders; D004298:Dopamine / Q000378:metabolism; D005260:Female; D005462:Fluorine Radioisotopes / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008694:Methamphetamine / Q000633:toxicity*; D008875:Middle Aged; D049268:Positron-Emission Tomography; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050637:Receptors, Dopamine D3 / Q000378:metabolism*; D012201:Reward; D011795:Surveys and Questionnaires; D055815:Young Adult
chemical_list: D001549:Benzamides; D000697:Central Nervous System Stimulants; D005462:Fluorine Radioisotopes; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D008694:Methamphetamine; C574003:fallypride; D004298:Dopamine
keywords: addiction; delay discounting; dopamine; impulsivity; positron emission tomography