Abstract
Drug cues, or conditioned responses to stimuli paired with drugs, are widely believed to promote drug use. The acquisition of these conditioned responses has been well characterized in laboratory animals: neutral stimuli paired with drugs elicit conditioned responses resembling the motivational and incentive properties of the drug itself. However, few studies have examined acquisition of conditioning, or the nature of the conditioned response, in humans. In this study, we used fMRI to examine neural responses to stimuli that had been paired with methamphetamine or placebo in healthy young adults. Participants first underwent four conditioning sessions in which visual-auditory stimuli were paired with either methamphetamine (20 mg, oral) or placebo. Then on a drug-free test day, the stimuli were presented during an fMRI scan to assess neural responses to the stimuli. We hypothesized that the stimuli would elicit drug-like brain activity, especially in regions related to reward. Instead, we found that the methamphetamine-paired stimuli, compared to placebo-paired stimuli, produced greater activation in regions related to visual and auditory processing, consistent with the drug’s unconditioned effects on sensory processing. This is the first study to demonstrate conditioned neural responses to drug-paired stimuli after just two pairings of methamphetamine in healthy adults. The study also illustrates that conditioned responses may develop to unexpected components of the drug’s effects.
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Acknowledgements
This research was supported by DA037011, and benefitted from S10OD018448 awarded to the University of Chicago MRI Research Center. Kathryne Van Hedger is currently supported by NIMH training grant T32MH020065. Dr. de Wit has received support unrelated to this study from the following sources: Consulting fees from Marinius and Jazz Pharmaceuticals; gift of a study drug from Indivior; and support for a research study from Insys Therapeutics.
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Van Hedger, K., Keedy, S.K., Mayo, L.M. et al. Neural responses to cues paired with methamphetamine in healthy volunteers. Neuropsychopharmacol 43, 1732–1737 (2018). https://doi.org/10.1038/s41386-017-0005-5
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DOI: https://doi.org/10.1038/s41386-017-0005-5
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