title: Reduced dopamine response to amphetamine in subjects at ultra-high risk for addiction.
abstract: BACKGROUND
  Not everyone who tries addictive drugs develops a substance use disorder. One of the best predictors of risk is a family history (FH) of substance use problems. In part, this might reflect perturbed mesolimbic dopamine responses.
  
  
  METHODS
  We measured amphetamine-induced changes in [(11)C]raclopride binding in 1) high-risk young adults with a multigenerational FH of substance use disorders (n = 16); 2) stimulant drug-naïve healthy control subjects with no known risk factors for addiction (n = 17); and 3) subjects matched to the high-risk group on personal drug use but without a FH of substance use problems (n = 15).
  
  
  RESULTS
  Compared with either control group, the high-risk young adults with a multigenerational FH of substance use disorders exhibited smaller [(11)C]raclopride responses, particularly within the right ventral striatum. Past drug use predicted the dopamine response also, but including it as a covariate increased the group differences.
  
  
  CONCLUSIONS
  Together, the results suggest that young people at familial high risk for substance use disorders have decreased dopamine responses to an amphetamine challenge, an effect that predates the onset of addiction.
authors.affiliation: Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec.
authors.forename: Kevin F
authors.initials: KF
authors.lastname: Casey
authors.affiliation: Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec; Department of Psychiatry, McGill University, Montreal, Quebec.
authors.forename: Chawki
authors.initials: C
authors.lastname: Benkelfat
authors.affiliation: Department of Psychology, McGill University, Montreal, Quebec.
authors.forename: Mariya V
authors.initials: MV
authors.lastname: Cherkasova
authors.affiliation: Department of Psychiatry, University of Alberta, Edmonton, Alberta.
authors.forename: Glen B
authors.initials: GB
authors.lastname: Baker
authors.affiliation: Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec.
authors.forename: Alain
authors.initials: A
authors.lastname: Dagher
authors.affiliation: Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec; Department of Psychology, McGill University, Montreal, Quebec; Department of Psychiatry, McGill University, Montreal, Quebec; Center for Studies in Behavioral Neurobiology (ML), Concordia University, Montreal, Quebec, Canada. Electronic address: marco.leyton@mcgill.ca.
authors.forename: Marco
authors.initials: M
authors.lastname: Leyton
mesh_terms: D000661:Amphetamine / Q000494:pharmacology*; D016022:Case-Control Studies; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists; D005192:Family Health; D005260:Female; D059907:Functional Neuroimaging; D006801:Humans; D008297:Male; D049268:Positron-Emission Tomography; D062706:Prodromal Symptoms; D020891:Raclopride; D019966:Substance-Related Disorders / Q000175:diagnosis* / Q000000981:diagnostic imaging; D055815:Young Adult
chemical_list: D000697:Central Nervous System Stimulants; D018492:Dopamine Antagonists; D020891:Raclopride; D000661:Amphetamine; D004298:Dopamine
keywords: Dopamine; PET; [(11)C]raclopride; stimulants; substance dependence; vulnerability