Abstract
Rationale
Contextual stimuli present during drug experiences become associated with the drug through Pavlovian conditioning and are thought to sustain drug-seeking behavior. Thus, extinction of conditioned responses is an important target for treatment. To date, acquisition and extinction to drug-paired cues have been studied in animal models or drug-dependent individuals, but rarely in non-drug users.
Objective
We have recently developed a procedure to study acquisition of conditioned responses after single doses of methamphetamine (MA) in healthy volunteers. Here, we examined extinction of these responses and their persistence after conditioning.
Methods
Healthy adults (18–35 years; N = 20) received two pairings of audio-visual stimuli with MA (20 mg oral) or placebo. Responses to stimuli were assessed before and after conditioning, using three tasks: behavioral preference, attentional bias, and subjective “liking.”
Results
Subjects exhibited behavioral preference for the drug-paired stimuli at the first post-conditioning test, but this declined rapidly on subsequent extinction tests. They also exhibited a bias to initially look towards the drug-paired stimuli at the first post-test session, but not thereafter. Subjects who experienced more positive subjective drug effects during conditioning exhibited a smaller decline in preference during the extinction phase. Further, longer inter-session intervals during the extinction phase were associated with less extinction of the behavioral preference measure.
Conclusions
Conditioned responses after two pairings with MA extinguish quickly, and are influenced by both subjective drug effects and the extinction interval. Characterizing and refining this conditioning procedure will aid in understanding the acquisition and extinction processes of drug-related conditioned responses in humans.
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Acknowledgements
The authors gratefully acknowledge contributions from Chris Boyson, Markus Heilig, and Leah Mayo and technical assistance from Austin Lee, Frances Enger, Alex Gura, Kristen Kitsch, Lauren Walker, and Maria Olex.
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This research was supported by DA037011. Dr. Cavallo was supported in part by a fellowship from the Clinical Pharmacology Fellowship Program in the University of Chicago Division of Biological Sciences.
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Cavallo, J.S., Ruiz, N.A. & de Wit, H. Extinction of Conditioned Responses to Methamphetamine-Associated Stimuli in Healthy Humans. Psychopharmacology 233, 2489–2502 (2016). https://doi.org/10.1007/s00213-016-4297-7
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DOI: https://doi.org/10.1007/s00213-016-4297-7