This project will examine the acquisition of conditioned drug-related responses in healthy adults. Conditioned drug cues are believe to play an important role in drug use, especially in relapse when they illicit drug-seeking behavior. Although numerous studies have demonstrated acquisition of conditioned drug cues in animal models, few studies have examined acquisition and expression of these responses in humans. To understand how conditioned stimuli acquire their powerful motivational force, we need to understand how they are acquired, how the conditioned responses are manifested (e.g., behavioral, physiological, neural), and how they persist. The knowledge gained will provide a translational link between the rich animal literature and the human clinical situation, and eventually allow us to target the learned responses as targets for addiction treatment. We have developed a novel procedure to study acquisition of Pavlovian conditioned responses in humans, showing that visual and auditory stimuli paired with a moderate dose of methamphetamine acquire positive incentive properties. Here, we propose to refine the procedure. We will measure the responses using sensitive measures of behavior, physiology, and brain activity using fMRI. We will determine the optimal parameters of conditioning, test the persistence and extinction of the conditioned response, and test the effects of the stimulus on emotional responses and neural activity using fMRI. Together, these studies will improve our understanding of how conditioning contributes to drug use, and provide a strong method and empirical basis to study conditioning with other drugs, the effects of potential treatment medications, and individual differences in cue reactivity.

Public Health Relevance

Conditioned, drug-associated cues are known to elicit craving and drug use in drug users, especially during relapse attempts. Although studies with laboratory animals indicate that these cues acquire salience through Pavlovian conditioning, this has yet to be demonstrated in humans. In collaboration with the Intramural Research Program at NIAAA, we have developed a procedure to study the acquisition and expression of conditioned, drug-associated responses in humans. Here, we will extend this finding to determine the parameters of acquisition and extinction, and to measure how these cues activate brain circuits involved in motivated behavior. This project will help us to understand how cues come to control craving and drug-seeking behavior, and identify the regions of the brain activated by drug cues.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Research Project (R01)
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Study Section
Risk, Prevention and Intervention for Addictions Study Section (RPIA)
Program Officer
Grant, Steven J
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University of Chicago
Schools of Medicine
United States
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de Wit, Harriet; Epstein, David H; Preston, Kenzie L (2018) Does human language limit translatability of clinical and preclinical addiction research? Neuropsychopharmacology 43:1985-1988
Van Hedger, Kathryne; Keedy, Sarah K; Mayo, Leah M et al. (2018) Neural responses to cues paired with methamphetamine in healthy volunteers. Neuropsychopharmacology 43:1732-1737
de Wit, Harriet; Sayette, Michael (2018) Considering the context: social factors in responses to drugs in humans. Psychopharmacology (Berl) 235:935-945
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Childs, Emma; de Wit, Harriet (2016) Alcohol-induced place conditioning in moderate social drinkers. Addiction 111:2157-2165
Cavallo, Joel S; Ruiz, Nicholas A; de Wit, Harriet (2016) Extinction of Conditioned Responses to Methamphetamine-Associated Stimuli in Healthy Humans. Psychopharmacology (Berl) 233:2489-502
Mayo, Leah M; de Wit, Harriet (2015) Acquisition of responses to a methamphetamine-associated cue in healthy humans: self-report, behavioral, and psychophysiological measures. Neuropsychopharmacology 40:1734-41