title: Levodopa effects on [ (11)C]raclopride binding in the resting human brain.
abstract: BACKGROUND
  Synaptic dopamine (DA) release induced by amphetamine or other experimental manipulations can displace [ (11)C]raclopride (RAC*) from dopamine D2-like receptors. We hypothesized that exogenous levodopa might increase dopamine release at striatal synapses under some conditions but not others, allowing a more naturalistic assessment of presynaptic dopaminergic function. Presynaptic dopaminergic abnormalities have been reported in Tourette syndrome (TS).
  
  
  OBJECTIVE
  Test whether levodopa induces measurable synaptic DA release in healthy people at rest, and gather pilot data in TS.
  
  
  METHODS
  This double-blind crossover study used RAC* and positron emission tomography (PET) to measure synaptic dopamine release 4 times in each of 10 carbidopa-pretreated, neuroleptic-naïve adults: before and during an infusion of levodopa on one day and placebo on another (in random order). Five subjects had TS and 5 were matched controls. RAC* binding potential (BP ND) was quantified in predefined anatomical volumes of interest (VOIs). A separate analysis compared BP ND voxel by voxel over the entire brain.
  
  
  RESULTS
  DA release declined between the first and second scan of each day (p=0.012), including on the placebo day. Levodopa did not significantly reduce striatal RAC* binding and striatal binding did not differ significantly between TS and control groups. However, levodopa's effect on DA release differed significantly in a right midbrain region (p=0.002, corrected), where levodopa displaced RAC* by 59% in control subjects but increased BP ND by 74% in TS subjects.
  
  
  CONCLUSIONS
  Decreased DA release on the second scan of the day is consistent with the few previous studies with a similar design, and may indicate habituation to study procedures. We hypothesize that mesostriatal DA neurons fire relatively little while subjects rest, possibly explaining the non-significant effect of levodopa on striatal RAC* binding. The modest sample size argues for caution in interpreting the group difference in midbrain DA release with levodopa.
authors.affiliation: Departments of Psychiatry, Neurology, Radiology, and Anatomy & Neurobiology, Washington University School of Medicine, St. Louis, MO, 63110, USA.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Black
authors.affiliation: School of Arts and Sciences, Washington University, St. Louis, MO, 63130, USA ; Temple University, Philadelphia, PA, USA.
authors.forename: Marilyn L
authors.initials: ML
authors.lastname: Piccirillo
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, 63110, USA.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Koller
authors.affiliation: School of Arts and Sciences, Washington University, St. Louis, MO, 63130, USA ; Department of Ophthalmology, University of Cincinnati, Cincinnati, OH, USA.
authors.forename: Tiffany
authors.initials: T
authors.lastname: Hseih
authors.affiliation: Departments of Psychiatry & Behavioral Sciences, and Radiology, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Departments of Radiology, Psychiatry, Bioengineering, and Anatomy & Neurobiology, Washington University, St. Louis, MO, 63130, USA ; Avid Radiopharmaceuticals, Philadelphia, PA, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Mintun
keywords: D2; PET; Tourette; accumbens; dopamine; emission; levodopa; midbrain; nigra; nucleus; positron; raclopride; receptor; substantia; syndrome; tomography