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Compulsive drug use linked to sensitized ventral striatal dopamine transmission.
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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“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
In the citing paper
“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
In the citing paper
“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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Metadata
- 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
- ORCID
- 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 › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Clinical Neurology › Deep Brain Stimulation and Movement Disorders
- 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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