Abstract
Classical conditioning is widely used to study motivational properties of addictive drugs in animals, but has rarely been used in humans. We established a procedure suitable for studying the neurobiology and individual determinants of classical conditioning in humans. Healthy volunteers were randomly assigned to four groups that received methamphetamine or placebo in the presence of distinctive environmental cues under paired or unpaired conditions. During each session, subjects performed tasks known to activate the ventral striatum. Tasks were performed in the presence of a distinctive context, consisting of a screen background image of a beach or mountains, accompanied by corresponding sounds. Separate groups of subjects carried out the tasks under high ($35–50) or low ($5–20) reward conditions. Within each of the two reward conditions, one group (paired) received methamphetamine (20 mg, oral) or placebo consistently associated with one of the contexts, while the other (unpaired) received drug or placebo unrelated to context. A fifth group (paired) performed the tasks with contextual cues but in the absence of monetary incentives. Before and after conditioning, participants carried out a series of forced choice tasks for the contextual cues, and change of preference over time was analyzed. All paired groups showed a significant increase in preference for the drug-associated context, with a linear trend for increase across the levels of reward. Preference was unrelated to subjective drug effects, and did not change in the unpaired group. These data support the translational utility of our conditioning procedure for studies of reward mechanisms in humans.
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Acknowledgements
This research was supported by the Division of Intramural Clinical and Biological Research NIAAA (MH) and by DA02812 (HdW). Leah Mayo was supported by T32 DA007255. We want to thank Dr Melanie Schwandt for data analysis and Mrs Karen Smith for assistance with the bibliography.
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HdW has received support from Unilever for a project unrelated to this research. MH is or has been the PI on Cooperative Research and Development Agreements between the NIH and Eli Lilly, Johnson & Johnson, Merck, Bristol Meyer Squibb, and GlaxoSmithKline unrelated to this project.
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Mayo, L., Fraser, D., Childs, E. et al. Conditioned Preference to a Methamphetamine-Associated Contextual Cue in Humans. Neuropsychopharmacol 38, 921–929 (2013). https://doi.org/10.1038/npp.2013.3
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DOI: https://doi.org/10.1038/npp.2013.3
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