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Amphetamine-induced dopamine release in Parkinson's disease patients with depression measured using high-resolution positron emission tomography with [¹¹C]raclopride Bogusz, Elliott Adam

Abstract

Depression affects around 40% of patients with Parkinson's disease (PD), which is nearly double the amount of severe depression seen in comparably disabled patients with other chronic illness. Mesocorticolimbic dopamine (DA) depletion has been implicated in the pathogenesis of depression, and thus may contribute to the high incidence of depression in PD. Amphetamine (AMPH)-induced striatal DA release was compared between depressed (n=3) and non-depressed (n=6) patients with PD using positron emission tomography. DA release was estimated by displacement of the D2/D3 receptor radiotracer [¹¹C]raclopride (RAC). Subjects completed three scans over two days within a three month period. The first scan was a baseline scan, followed by either blinded d-AMPH (0.3 mg/kg p.o.) or placebo administration, counterbalanced across subjects. Emission data were acquired for 60 minutes using a high resolution research tomograph, scans were reconstructed using Ordinary Poisson-OSEM3D including attenuation, scatter and random correction, and inter-frame realignment was performed to correct for motion. RAC binding potentials were estimated using regions of interest and a graphical tissue approach with the cerebellum as a reference region. Amphetamine induced DA release was observed at a significant level in the ventral striatum and with a strong trend in the caudate. Although amphetamine induced DA release has been observed in other studies, these PD patients exhibit a different amphetamine induced profile in which caudate and ventral DA release was greater than putamen DA release. No significant placebo effect was measured in this study but visual inspection suggests depressed patients may have a decrease in endogenous DA release with placebo. Other than this effect no difference was observed between depressed and non-depressed PD subjects. Ongoing work will attempt to extend these findings to a larger sample.

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