Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Apr 19;26(8):3866.
doi: 10.3390/ijms26083866.

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

Megan A Aumann  1 , Sean J Lee  1 , Alexander K Song  1 , Kaitlyn R O'Rourke  1 , Paula Trujillo  1 , Yan Yan  2 , Hakmook Kang  2 , Daniel O Claassen  1
Affiliations

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

Megan A Aumann et al. Int J Mol Sci. .

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.

Keywords: Parkinson’s; amphetamine; dopamine; fallypride; impulsivity; mood.

PubMed Disclaimer

Conflict of interest statement

The authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. P.T. is a paid consultant for Alterity. D.O.C. receives support for research from the Huntington’s Disease Society of America, the Griffin Foundation, the National Institute of Neurological Disorders and Stroke, National Institute on Aging, and the National Center for Complementary and Integrative Health. He received pharmaceutical grant support from AbbVie, Biogen, Acadia, Cerecour, BMS, PTC Therapeutics, Eli Lilly, Genetech/Roche, Lundbeck, Jazz Pharmaceuticals, Spark, Wave Life Sciences, Teva Neuroscience, and Vaccinex. Currently, he receives grant support from Genentech/Roche, AbbVie, Prilenia, PTC Therapeutics, Alterity, AbbVie, and CHDI, and he has served as a consultant to or on the advisory board of Alterity, Teva Neuroscience, Neurocrine, Adamas, Acadia, Lundbeck, and Photopharmics.

Figures

Figure 1
Figure 1
Box-and-whisker plots showing the median and quartile distribution for PANAS positive scores in all PD subjects (left) and split into PD-ICB (middle) and PD-C cohorts (right) in both off-dAMPH (blue) and on-dAMPH (red) conditions. ** Indicates statistically significant results after multiple comparisons correction at p < 0.05, and *** at p < 0.01.
Figure 2
Figure 2
Box-and-whisker plots showing the median and quartile distribution for all PD subjects (left) and split into PD-ICB (middle) and PD-C cohorts (right) in both off-dAMPH (blue) and on-dAMPH (red) conditions for AIRS total (A), AIRS activation (B), AIRS physical (C), and AIRS euphoria (D) scores. * Indicates statistically significant results after multiple comparisons correction at p < 0.1 and ** at p < 0.05. # Indicates results significant at p < 0.05 before multiple comparisons correction.
Figure 3
Figure 3
Box-and-whisker plots showing the median and quartile distribution for all PD subjects (left) and split into PD-ICB (middle) and PD-C cohorts (right) in both off-dAMPH (blue) and on-dAMPH (red) conditions for DEQ feel (A) and DEQ high (B) scores. * Indicates statistically significant results after multiple comparisons correction at p < 0.1. Spearman correlation indicating the relationship between change in AIRS depression scores, defined as (off-dAMPH–on-dAMPH)/off-dAMPH, related to QUIP-RS across all PD subjects.
Figure 4
Figure 4
T1-weighted (T1w) magnetic resonance image (MRI) for anatomical reference associated with PET BPND maps in the amphetamine (ON dAMPH) and baseline (OFF dAMPH) conditions for both Parkinson’s patients without impulsive–compulsive behaviors (PD-C; top row) and with impulsive–compulsive behaviors (PD-ICB; bottom row). The average change in BPND for each group is shown on the far right as Δ BPND (OFF-ON dAMPH).
Figure 5
Figure 5
Spearman correlation indicating the relationship between change in PANAS positive scores, defined as (off-dAMPH-on-dAMPH)/off-dAMPH, related to baseline binding potential (BP) across all PD subjects for the amygdala (A), caudate (B), and ventral striatum (VS) (C). Blue dots indicate individual subjects; solid blue line indicates regression line; red dotted lines indicate 95% confidence interval.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Ahearn D.J., McDonald K., Barraclough M., Leroi I. An exploration of apathy and impulsivity in Parkinson disease. Curr. Gerontol. Geriatr. Res. 2012;2012:390701. doi: 10.1155/2012/390701. - DOI - PMC - PubMed
    1. Wen M.C., Chan L.L., Tan E.K. Depression, anxiety, and apathy in Parkinson’s disease: Insights from neuroimaging studies. Eur. J. Neurol. 2016;23:1001–1019. doi: 10.1111/ene.13002. - DOI - PMC - PubMed
    1. Menza M.A., Sage J., Marshall E., Cody R., Duvoisin R. Mood changes and ‘on-off’ phenomena in Parkinson’s disease. Mov. Disord. 1990;5:148–151. doi: 10.1002/mds.870050210. - DOI - PubMed
    1. Weiss H.D., Marsh L. Impulse control disorders and compulsive behaviors associated with dopaminergic therapies in Parkinson disease. Neurol. Clin. Pract. 2012;2:267–274. doi: 10.1212/CPJ.0b013e318278be9b. - DOI - PMC - PubMed
    1. Ambermoon P., Carter A., Hall W.D., Dissanayaka N.N.W., O’Sullivan J.D. Impulse control disorders in patients with Parkinson’s disease receiving dopamine replacement therapy: Evidence and implications for the addictions field. Addiction. 2011;106:283–293. doi: 10.1111/j.1360-0443.2010.03218.x. - DOI - PubMed

MeSH terms

LinkOut - more resources