Abstract
One known risk factor for drug use and abuse is sensitivity to rewarding effects of drugs. It is not known whether this risk factor extends to sensitivity to non-drug rewards. In this study with healthy young adults, we examined the association between sensitivity to the subjective rewarding effects of amphetamine and a neural indicator of anticipation of monetary reward. We hypothesized that greater euphorigenic response to amphetamine would be associated with greater neural activation to anticipation of monetary reward (Win > Loss). Healthy participants (N = 61) completed four laboratory sessions in which they received d-amphetamine (20 mg) and placebo in alternating order, providing self-report measures of euphoria and stimulation at regular intervals. At a separate visit 1–3 weeks later, participants completed the guessing reward task (GRT) during fMRI in a drug-free state. Participants reporting greater euphoria after amphetamine also exhibited greater neural activation during monetary reward anticipation in mesolimbic reward regions, including the bilateral caudate and putamen. This is the first study to show a relationship between neural correlates of monetary reward and sensitivity to the subjective rewarding effects of amphetamine in humans. These findings support growing evidence that sensitivity to reward in general is a risk factor for drug use and abuse, and suggest that sensitivity of drug-induced euphoria may reflect a general sensitivity to rewards. This may be an index of vulnerability for drug use or abuse.
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Notes
After extracting parameter estimates/β-weights from the peak activation, we found that one participant’s BOLD peak activation was an outlier (see Fig. 3b). Therefore, we re-ran the second-level model in SPM without this participant (n = 60) and the results remained significant.
In addition to including motion time series in the first-level GLM, we ran the second-level GLM with average framewise displacement for each participant as a covariate and the results remained significant.
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Funding
This publication was funded by the National Institute on Drug Abuse (NIDA) (R01DA002812, PIs: H.d.W. and K.L.P.). S.M.G. was supported by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) (K23AA025111, PI: S.M.G.) and J.W. was supported by NIAAA (K01AA024519, PI: J.W.). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of NIDA, NIAAA, or the National Institutes of Health.
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H.d.W. received consulting fees from Jazz Pharmaceuticals, research support in the form of a GRAND award from Pfizer, support for a research study from Insys Therapeutics, and a donation of a research drug from Indivior. None of these were related to the research reported here. All the other authors declare no competing interests.
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Crane, N.A., Gorka, S.M., Weafer, J. et al. Neural activation to monetary reward is associated with amphetamine reward sensitivity. Neuropsychopharmacol 43, 1738–1744 (2018). https://doi.org/10.1038/s41386-018-0042-8
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DOI: https://doi.org/10.1038/s41386-018-0042-8
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