title: Effects of lowered serotonin transmission on cocaine-induced striatal dopamine response: PET [¹¹C]raclopride study in humans.
abstract: BACKGROUND
  Low serotonin transmission is thought to increase susceptibility to a wide range of substance use disorders and impulsive traits.
  
  
  OBJECTIVE
  To investigate the effects of lowered serotonin on cocaine-induced (1.0 mg/kg cocaine, self-administered intranasally) dopamine responses and drug craving.
  
  
  METHODS
  In non-dependent cocaine users, serotonin transmission was reduced using the acute tryptophan depletion method. Striatal dopamine responses were measured using positron emission tomography with [(11)C]raclopride.
  
  
  RESULTS
  Acute tryptophan depletion increased drug craving and striatal dopamine responses to cocaine. These acute tryptophan depletion-induced increases did not occur in the absence of cocaine.
  
  
  CONCLUSIONS
  The results suggest that low serotonin transmission can increase dopaminergic and appetitive responses to cocaine. These findings might identify a mechanism by which individuals with low serotonin are at elevated risk for both substance use disorders and comorbid conditions.
authors.affiliation: Department of Psychiatry, McGill University, Montreal, Quebec, Canada.
authors.forename: Sylvia M L
authors.initials: SM
authors.lastname: Cox
authors.forename: Chawki
authors.initials: C
authors.lastname: Benkelfat
authors.forename: Alain
authors.initials: A
authors.lastname: Dagher
authors.forename: J Scott
authors.initials: JS
authors.lastname: Delaney
authors.forename: France
authors.initials: F
authors.lastname: Durand
authors.forename: Theodore
authors.initials: T
authors.lastname: Kolivakis
authors.forename: Kevin F
authors.initials: KF
authors.lastname: Casey
authors.forename: Marco
authors.initials: M
authors.lastname: Leyton
mesh_terms: D000281:Administration, Intranasal; D000328:Adult; D000704:Analysis of Variance; D003042:Cocaine / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000523:psychology; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods; D020891:Raclopride / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D012701:Serotonin / Q000378:metabolism*; D014364:Tryptophan / Q000008:administration & dosage / Q000172:deficiency / Q000378:metabolism; D055815:Young Adult
chemical_list: D018765:Dopamine Uptake Inhibitors; D019275:Radiopharmaceuticals; D012701:Serotonin; D020891:Raclopride; D014364:Tryptophan; D003042:Cocaine; D004298:Dopamine