F1000Research Open Peer Review , Hôpital Pitié Salpêtrière Marie Vidailhet France , University of Alberta W.R. Wayne Martin Canada , Umeå Center for Functional Lars Nyberg Brain Imaging Sweden Discuss this article (3) Comments 3 2 1 RESEARCH ARTICLE Levodopa effects on [ C]raclopride binding in the resting human brain [v1; ref status: indexed, http://f1000r.es/4oe] Kevin J. Black , Marilyn L. Piccirillo , Jonathan M. Koller , Tiffany Hseih , Lei Wang , Mark A. Mintun 5,8 Departments of Psychiatry, Neurology, Radiology, and Anatomy & Neurobiology, Washington University School of Medicine, St. Louis, MO, 63110, USA School of Arts and Sciences, Washington University, St. Louis, MO, 63130, USA Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, 63110, USA Departments of Psychiatry & Behavioral Sciences, and Radiology, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA Departments of Radiology, Psychiatry, Bioengineering, and Anatomy & Neurobiology, Washington University, St. Louis, MO, 63130, USA Temple University, Philadelphia, PA, USA Department of Ophthalmology, University of Cincinnati, Cincinnati, OH, USA Avid Radiopharmaceuticals, Philadelphia, PA, USA Abstract Synaptic dopamine (DA) release induced by amphetamine or other Rationale: experimental manipulations can displace [ 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). Test whether levodopa induces measurable synaptic DA release in Objective: healthy people at rest, and gather pilot data in TS. This double-blind crossover study used RAC* and positron emission Methods: 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 ) was quantified in predefined anatomical volumes of interest (VOIs). A separate analysis compared BP voxel by voxel over the entire brain. DA release declined between the first and second scan of each day Results: (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 BP by 74% in TS increased subjects. Decreased DA release on the second scan of the day is Discussion: 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 11 1 2,6 3 2,7 4 5,8 1 2 3 4 5 6 7 8 Referee Status: Invited Referees version 1 published 23 Jan 2015 1 2 3 report report report 23 Jan 2015, :23 (doi: ) First published: 4 10.12688/f1000research.5672.1 23 Jan 2015, :23 (doi: ) Latest published: 4 10.12688/f1000research.5672.1 v1 11 ND ND ND Page 1 of 17 F1000Research 2015, 4:23 Last updated: 07 JUL 2015