Cited by 473Parkinson's Disease Mechanisms and TreatmentsNeurotransmitter Receptor Influence on BehaviorNeurological disorders and treatments

Compulsive drug use linked to sensitized ventral striatal dopamine transmission.

Evans, Andrew H., Pavese, Nicola, Lawrence, Andrew D., Tai, Yen F., Appel, Silke, Doder, Miroslava, Brooks, David J., Lees, Andrew J. +1 more·2006·Annals of Neurology

Abstract

OBJECTIVE: A small group of Parkinson's disease (PD) patients compulsively use dopaminergic drugs despite causing harmful social, psychological, and physical effects and fulfil core Diagnostic and Statistical Manual (of Mental Disorders) Fourth Edition criteria for substance dependence (dopamine dysregulation syndrome [DDS]). We aimed to evaluate levodopa-induced dopamine neurotransmission in the striatum of patients with DDS compared with PD control patients. METHODS: We used a two-scan positron emission tomography protocol to calculate the percentage change in (11)C-raclopride binding potential from a baseline withdrawal (off drug) state to the binding potential after an oral dose of levodopa. We related the subjective effects of levodopa to the effects on endogenous dopamine release of a pharmacological challenge with levodopa in eight control PD patients and eight patients with DDS. RESULTS: PD patients with DDS exhibited enhanced levodopa-induced ventral striatal dopamine release compared with levodopa-treated patients with PD not compulsively taking dopaminergic drugs. The sensitized ventral striatal dopamine neurotransmission produced by levodopa in these individuals correlated with self-reported compulsive drug "wanting" but not "liking" and was related to heightened psychomotor activation (punding). INTERPRETATION: This provides evidence that links sensitization of ventral striatal circuitry in humans to compulsive drug use.

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Crossref · 10.1002/ana.20822

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  • Increases of human dopamine do not reliably cause enhancement of subjective ratings of pleasure.

    “Similarly, it is now increasingly clear that increases of human dopamine do not reliably cause enhancement of subjective ratings of pleasure (although many rewards do induce dopamine release as a consequence and correlate, but not the cause, of pleasure) (Leyton et al., 2002; Evans et al., 2006; Liggins et al., 2012).”

    From Evolving Concepts of Emotion and Motivation (2018) · cites this paper as Evans et al., 2006

  • Dopamine surges in nucleus accumbens evoked by addictive amphetamine or by L-DOPA correlate poorly with human subjective liking ratings of the drug, but do control their subjective wanting ratings to take more of that drug.

    “Dopamine surges in nucleus accumbens evoked by addictive amphetamine or by L-DOPA correlate poorly with human subjective liking ratings of the drug - but do control their subjective wanting ratings to take more of that drug (Leyton et al., 2002; Evans et al., 2006).”

    From Evolving Concepts of Emotion and Motivation (2018) · cites this paper as Evans et al., 2006

  • Many rewards induce dopamine release as a consequence and correlate, but not the cause, of pleasure.

    “Similarly, it is now increasingly clear that increases of human dopamine do not reliably cause enhancement of subjective ratings of pleasure (although many rewards do induce dopamine release as a consequence and correlate, but not the cause, of pleasure) (Leyton et al., 2002; Evans et al., 2006; Liggins et al., 2012).”

    From Evolving Concepts of Emotion and Motivation (2018) · cites this paper as Evans et al., 2006

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Authors
Evans, A. H., Pavese, N., Lawrence, A. D., Tai, Y. F., Appel, S., Doder, M., Brooks, D. J., Lees, A. J., & Piccini, P.
Affiliations
  • National Hospital for Neurology and Neurosurgery (GB)
  • Hammersmith Hospital (GB)
  • MRC Cognition and Brain Sciences Unit (GB)
Corresponding author
Piccini, Paola
Venue
Annals of Neurology
Publisher
Wiley
Published
2006-03-23
Volume
59
Issue
5
Pages
852-858
ISSN
  • 0364-5134 (ISSN-L)
  • 1531-8249
OpenAlex
W2115622614
Cited by
473
References
52
Citations by year
2026: 6 · 2025: 5 · 2024: 11 · 2023: 8 · 2022: 15 · 2021: 17 · 2020: 76 · 2019: 10 · 2018: 25 · 2017: 20 · 2016: 17 · 2015: 30 · 2014: 23 · 2013: 30 · 2012: 30
FWCI
15.54
Type
journal article
Language
en
Open access
closed
Locations
  • Annals of Neurology (publishedVersion)
  • PubMed (publishedVersion)
  • UCL Discovery (University College London) (submittedVersion)
Topics
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Health Sciences › Medicine › Neurology › Neurological disorders and treatments
Keywords
dopamine dysregulation syndrome, compulsive drug use, Parkinson's disease, ventral striatum, dopamine signaling, levodopa challenge, dopamine release, punding, drug liking, substance dependence
MeSH terms
Aged, Brain Mapping, Dopamine, Exploratory Behavior, Female, Humans, Levodopa, Male, Middle Aged, Synaptic Transmission, Psychological Tests, Dopamine Agents, Neostriatum, Receptors, Dopamine D2, Dopamine Antagonists, Substance-Related Disorders, Raclopride, Positron-Emission Tomography, Receptors, Dopamine D3

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