Behavioral Effects of Stimulated Dopamine Release and D2-like Receptor Displacement in Parkinson’s Patients with Impulse-Control Disorder

TL;DR

This study explores how dopamine release affects mood in Parkinson’s patients, finding that those with impulsive behaviors react more strongly to dopamine stimulation.

Contribution

The study identifies specific brain regions and dopamine pathways linked to mood changes in Parkinson’s patients with impulsive behaviors.

Findings

Dopamine stimulation increased positive mood and arousal in all Parkinson’s patients.

Patients with impulsive behaviors showed greater mood increases after dopamine stimulation.

Dopamine receptor availability in key brain regions correlated with mood responses.

Abstract

Dysregulated dopamine (DA) release in the mesocorticolimbic circuit is noted in Parkinson’s disease (PD) patients with impulsive and compulsive behaviors (ICBs). However, the effect of acute DA release on mood, the localization of this process, and the phenotypic differences in patients with ICB remain unknown. We applied a placebo-controlled dextro-amphetamine (dAMPH) study in 20 PD patients: 10 with ICBs (PD-ICB) and 10 without (PD-C). Subjective mood experiences were measured with well-described self-reported measures including the Positive and Negative Affect Scale (PANAS), Drug Effects Questionnaire (DEQ), and Amphetamine Interview Rating Scale (AIRS). D2-like receptor availability was measured as non-displaceable binding potential (BPND) using PET imaging with the high-affinity D2/3 receptor ligand [18F]-fallypride. Among all the subjects, dAMPH increased the PANAS positive, DEQ feel, DEQ high, and AIRS total scores. Increases in the PANAS positive and AIRS total scores were greater in the PD-ICB cohort. A mixed-effects model correlated these questionnaire changes with dAMPH-induced reductions in BPND in the ventral striatum (VS), caudate, amygdala, and caudo-medial orbitofrontal cortex. The baseline caudate, VS, and amygdala BPND positively correlated with lower on-dAMPH PANAS positive scores. Elevated mood symptoms of acute dAMPH administration in PD are linked to DA release in the mesocorticolimbic regions. Distinctions in behavioral effects among PD-ICB subjects emphasize that dysregulated striatal and extra-striatal DA-ergic networks alter mood responses to stimulated DA release and may also contribute to behavioral changes resulting from DA-targeting therapies in PD.

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