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

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 [11C]-(+)-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 [11C]-(+)-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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Acknowledgements

We thank Alvina Ng, Laura Nguyen, Armando Garcia, Winston Stableford and Min Wong for excellent technical assistance.

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Correspondence to M Zack.

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This project is funded in part by the Ontario Problem Gambling Research Centre (MZ, IB, DL). MZ receives funds from the Canadian Institutes of Health Research and Ontario Brain Institute. IB received an Investigator Award from the Ontario Mental Health Foundation and funds from the Canadian Institute of Health Research and the National Institute of Health (NIDA). SK receives funds from the National Institute of Health (NIDA). SH received funds from the Canada Foundation for Innovation and Ontario Research Funds. DP, BS, DSSL, JW and AW report no financial relationships with commercial interests.

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Boileau, I., Payer, D., Chugani, B. et al. In vivo evidence for greater amphetamine-induced dopamine release in pathological gambling: a positron emission tomography study with [11C]-(+)-PHNO. Mol Psychiatry 19, 1305–1313 (2014). https://doi.org/10.1038/mp.2013.163

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