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F1000Res. 2015 Jan 23;4:23. doi: 10.12688/f1000research.5672.1. eCollection 2015.

Levodopa effects on [ (11)C]raclopride binding in the resting human brain.

Author information

1
Departments of Psychiatry, Neurology, Radiology, and Anatomy & Neurobiology, Washington University School of Medicine, St. Louis, MO, 63110, USA.
2
School of Arts and Sciences, Washington University, St. Louis, MO, 63130, USA ; Temple University, Philadelphia, PA, USA.
3
Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, 63110, USA.
4
School of Arts and Sciences, Washington University, St. Louis, MO, 63130, USA ; Department of Ophthalmology, University of Cincinnati, Cincinnati, OH, USA.
5
Departments of Psychiatry & Behavioral Sciences, and Radiology, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA.
6
Departments of Radiology, Psychiatry, Bioengineering, and Anatomy & Neurobiology, Washington University, St. Louis, MO, 63130, USA ; Avid Radiopharmaceuticals, Philadelphia, PA, USA.

Abstract

RATIONALE:

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.

DISCUSSION:

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.

KEYWORDS:

D2; PET; Tourette; accumbens; dopamine; emission; levodopa; midbrain; nigra; nucleus; positron; raclopride; receptor; substantia; syndrome; tomography

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