Abstract
Rationale
Stimulant drugs like methamphetamine (MA) activate brain reward circuitry, which is linked to the development of problematic drug use. It is not clear how drugs like MA alter neural response to a non-drug reward.
Objectives
We examined how acute MA impacts neural response to receipt of a monetary reward relative to a loss in healthy adults. We hypothesized that MA (vs. placebo) would increase mesolimbic neural activation to reward, relative to loss.
Methods
In a within-subject, randomized, cross-over, double-blind, placebo-controlled design, 41 healthy adults completed the Doors monetary reward task during fMRI after ingestion of placebo or 20 mg MA. We examined drug effects on neural response to reward receipt (Win vs. Loss) using a priori anatomical striatal regions of interest (nucleus accumbens (NAcc), caudate, putamen).
Results
MA decreased NAcc BOLD activation to reward vs loss compared to placebo (p=.007) without altering caudate or putamen BOLD activation. Similar effects for reward vs. loss were obtained using whole brain analysis. Additional exploratory ROI analysis comparing reward and loss activation relative to a neutral “fixation” period indicated that MA increased NAcc BOLD activation during loss trials, without decreasing activation during win trials.
Conclusions
This preliminary evidence suggests that MA increases NAcc neural response to the receipt of monetary loss. Additional studies are needed to replicate our findings and clarify the mechanisms contributing to altered mesolimbic neural response to reward and loss receipt during stimulant intoxication.
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The contents of the paper are solely the responsibility of the authors and do not necessarily represent the official views of NIDA, NIGMS, or the National Institutes of Health.
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This publication was funded by the National Institute on Drug Abuse (NIDA) (R01DA002812, PI: HdW). NAC was supported by NIDA (K23DA048132, PI: NAC). HM was supported by the National Institute of General Medical Sciences (NIGMS) (T32GM07019). Dr. de Wit has served on Scientific Advisory committees for Gilgamesh Pharmaceuticals, Awakn Life Sciences and MIND Foundation, and she is on the Board of Directors of PharmAla Biotech.
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All authors have participated sufficiently in the work and take responsibility for authorship and publication. NAC conducted the statistical analyses, interpreted the data, and wrote the initial draft of the paper. HM made substantial contributions to the data analysis and writing of the manuscript. HDW was the principal investigator of the study, contributed to the conceptual design of the study, made important contributions to the editing of the paper, and assisted in data interpretation.
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Crane, N.A., Molla, H. & de Wit, H. Methamphetamine alters nucleus accumbens neural activation to monetary loss in healthy young adults. Psychopharmacology 240, 1891–1900 (2023). https://doi.org/10.1007/s00213-023-06398-4
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DOI: https://doi.org/10.1007/s00213-023-06398-4