In vivo evidence for greater amphetamine-induced dopamine release in pathological gambling: a positron emission tomography study with [11C]-(+)-PHNO

Boileau, I; Payer, D; Chugani, B; Lobo, D S S; Houle, S; Wilson, A A; Warsh, J; Kish, S J; Zack, M

doi:10.1038/mp.2013.163

Cited by 198Gambling Behavior and TreatmentsNeurotransmitter Receptor Influence on BehaviorObsessive-Compulsive Spectrum Disorders

In vivo evidence for greater amphetamine-induced dopamine release in pathological gambling: a positron emission tomography study with [11C]-(+)-PHNO

Boileau, I, Payer, D, Chugani, B, Lobo, D S S, Houle, S, Wilson, A A, Warsh, J, Kish, S J +1 more·2014·Molecular Psychiatry

DOI 10.1038/mp.2013.163

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Abstract

Drug addiction has been associated with deficits in mesostriatal dopamine (DA) function, but whether this state extends to behavioral addictions such as pathological gambling (PG) is unclear. Here we used positron emission tomography and the D3 receptor-preferring radioligand [(11)C]-(+)-PHNO during a dual-scan protocol to investigate DA release in response to oral amphetamine in pathological gamblers (n=12) and healthy controls (n=11). In contrast with human neuroimaging findings in drug addiction, we report the first evidence that PG is associated with greater DA release in dorsal striatum (54-63% greater [(11)C]-(+)-PHNO displacement) than controls. Importantly, dopaminergic response to amphetamine in gamblers was positively predicted by D3 receptor levels (measured in substantia nigra), and related to gambling severity, allowing for construction of a mechanistic model that could help explain DA contributions to PG. Our results are consistent with a hyperdopaminergic state in PG, and support the hypothesis that dopaminergic sensitization involving D3-related mechanisms might contribute to the pathophysiology of behavioral addictions.

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Sensitization of mesolimbic dopamine function results in the amplification of the neural mechanisms for incentive salience that transform ordinary levels of cue-triggered 'wanting' into excessive levels of urges to take drugs and gamble, and a persistent vulnerability to relapse.
“Sensitization of mesolimbic dopamine function results in the amplification of the neural mechanisms for incentive salience that transform ordinary levels of cue-triggered ‘wanting’ into excessive levels of urges to take drugs and gamble, and a persistent vulnerability to relapse (Boileau et al., 2014; W. Y. Kim, Cho, Kwak, & Kim, 2017; Leyton, 2007).”
From Cued for Risk: Evidence for an Incentive Sensitization Framework to Explain the Interplay between Stress and Anxiety, Substance Abuse, and Reward Uncertainty in Disordered Gambling Behavior (2019) · cites this paper as Boileau et al., 2014
Problem gamblers have increased dopamine release in their dorsal striatum in response to amphetamine in comparison with healthy controls.
“Boileau and colleagues found that problem gamblers have increased dopamine release in their dorsal striatum in response to amphetamine in comparison with healthy controls (Boileau et al., 2014).”
From Cued for Risk: Evidence for an Incentive Sensitization Framework to Explain the Interplay between Stress and Anxiety, Substance Abuse, and Reward Uncertainty in Disordered Gambling Behavior (2019) · cites this paper as Boileau et al., 2014
There is evidence for cross-sensitization between drugs of abuse and gambling.
“There is also evidence for cross-sensitization between drugs of abuse and gambling (Boileau et al., 2014; Mascia et al., 2018; Singer, Scott-Railton, & Vezina, 2012; Zack, Featherstone, Mathewson, & Fletcher, 2014; Zeeb et al., 2017)”
From Cued for Risk: Evidence for an Incentive Sensitization Framework to Explain the Interplay between Stress and Anxiety, Substance Abuse, and Reward Uncertainty in Disordered Gambling Behavior (2019) · cites this paper as Boileau et al., 2014

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Authors: Boileau, I., Payer, D., Chugani, B., Lobo, D. S. S., Houle, S., Wilson, A. A., Warsh, J., Kish, S. J., & Zack, M.
Affiliations: Centre for Addiction and Mental Health (CA)
University of Toronto (CA)
Corresponding author: Zack, M
ORCID: Boileau, I
Payer, D
Chugani, B
Lobo, D S S
Houle, S
Warsh, J
Kish, S J
Zack, M
Venue: Molecular Psychiatry
Publisher: Springer Science and Business Media LLC
Published: 2013-12-10
Volume: 19
Issue: 12
Pages: 1305-1313
ISSN: 1359-4184 (ISSN-L)
1476-5578
DOI: 10.1038/mp.2013.163
OpenAlex: W1989017766
Cited by: 198
References: 76
Citations by year: 2026: 1 · 2025: 6 · 2024: 6 · 2023: 10 · 2022: 8 · 2021: 9 · 2020: 53 · 2019: 14 · 2018: 16 · 2017: 12 · 2016: 21 · 2015: 28 · 2014: 14
FWCI: 23.34
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Molecular Psychiatry (publishedVersion)
PubMed (publishedVersion)
Funders: Canadian Institutes of Health Research
Topics: Social Sciences › Psychology › Clinical Psychology › Gambling Behavior and Treatments
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Social Sciences › Psychology › Clinical Psychology › Obsessive-Compulsive Spectrum Disorders
Keywords: gambling addiction, dopamine release, amphetamine challenge, dopamine D3 receptor, [11C]-(+)-PHNO, dorsal striatum, substantia nigra, hyperdopaminergic state, behavioral addiction, gambling severity
MeSH terms: Adult, Amphetamine, Brain, Dopamine, Gambling, Humans, Male, Models, Neurological, Oxazines, Severity of Illness Index, Dopamine Agents, Dopamine Agonists, Radiopharmaceuticals, Positron-Emission Tomography, Receptors, Dopamine D3

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In vivo evidence for greater amphetamine-induced dopamine release in pathological gambling: a positron emission tomography study with [11C]-(+)-PHNO

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