Objective: To evaluate behavioral effects of stimulated dopamine (DA) release in Parkinson’s disease (PD) by assessing D_2/3 receptor (DA-R) displacement on PET imaging

Background: Previous studies suggest that PD patients with impulsive-compulsive behaviors (ICB) have altered DA release along the mesocorticolimbic pathway. Here we evaluated the effect of d-amphetamine (dAMPH) on mood and DA-R availability in a cohort of PD patients with and without ICB.

Method: 20 PD patients, 10 with ICB, underwent [¹⁸F]-fallypride PET scans in a within-subject, single-blinded, placebo-controlled dAMPH study. All completed the Questionnaire for ICB disorders in PD (QUIP-RS) and behavioral interview at baseline. Subjective experiences off- and on-dAMPH were assessed with the Positive and Negative Affect Scale (PANAS), Drug Effects Questionnaire (DEQ), and Amphetamine Interview Rating Scale (AIRS). D_2/3 non-displaceable binding potential (BP_ND) was assessed in 10 a priori regions of interest; change in BP_ND was interpreted as DA release.

Results: dAMPH increased PANAS positive (p = 0.0001), DEQ feel (p = 0.019), DEQ high (p = 0.033), and AIRS TOTAL (p = 0.004) ratings. In response to dAMPH, ICB+ patients had greater AIRS TOTAL (p = 0.041); ICB- patients had elevated DEQ high (p = 0.037) and AIRS physical (p = 0.036) scores. Baseline QUIP-RS correlated positively with dAMPH-induced increases in AIRS depression (p = 0.046; R² = 0.19). These effects were associated with dAMPH-induced reductions in BP_ND in caudate, ventral striatum (VS), amygdala, ventromedial orbitofrontal cortex (vmOFC), and insula. Baseline BP_ND in amygdala (p = 0.018; R² = 0.36), caudate (p = 0.027; R² = 0.33), and VS (p = 0.016; R² = 0.37) correlated with a lower PANAS positive score on-dAMPH. Baseline BP_ND in putamen correlated with lower AIRS TOTAL (p = 0.036; R² = 0.40) and AIRS euphoria (p = 0.048; R² = 0.26) scores on-dAMPH.

Conclusion: Positive mood effects of acute dAMPH administration in PD are linked to stimulated DA release in mesocorticolimbic regions. Distinctions in behavioral effects of dAMPH in ICB+ patients emphasize that impulsivity is related to differing perceptions of mood response to stimulated DA release. These differences may account for the emergence of behavioral changes resulting from DA therapies in PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/behavioral-effects-of-stimulated-dopamine-release-and-d2-like-receptor-displacement-in-parkinsons-patients-with-impulse-control-disorder/