Levodopa effects on [ C]raclopride binding in the resting human brain [version 1; referees: 3 approved]

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