Acquisition of Responses to a Methamphetamine-Associated Cue in Healthy Humans: Self-Report, Behavioral, and Psychophysiological Measures

Abstract

Drug-associated cues elicit conditioned responses in human drug users, and are thought to facilitate a drug-seeking behavior. Yet, little is known about how these associations are acquired, or about the specificity of the conditioned response modalities. In this study, healthy, nondependent volunteers (N ¼ 90) completed a conditioning paradigm in which they received a moderate dose of methamphetamine paired with one stimulus and placebo with another stimulus, each on two separate occasions. Their responses to these cues were measured with a behavioral preference, self-reported 'liking', emotional reactivity, and attentional bias measures, both before and after the conditioning. Following the conditioning procedure, subjects exhibited a behavioral preference, positive emotional reactivity, and attentional bias toward the methamphetamine-associated cue, compared with the placebo stimulus. In addition, subjects who reported greater positive subjective drug effects during the conditioning displayed a more robust conditioning. This work demonstrates that healthy nondependent volunteers readily acquire conditioned responses to neutral stimuli paired with a drug. The procedure has significant value to study individual variation in acquisition of conditioned responses as a possible risk factor for drug taking, and to study the neural basis of conditioned drug responses.

Acquisition of Conditioned Responses to a Novel Alcohol-Paired Cue in Social Drinkers

“…However, conditioning was not detected with outcome measures of behavioral preference or emotional reactivity (as measured by zygomatic or corrugator reactivity). These results contrast with our previous findings with methamphetamine (Mayo & de Wit, 2015), in which conditioning produced responses according to measures of behavioral preference, emotional reactivity, and attention. Thus, at this dose of alcohol and in this sample of participants, conditioning with alcohol was less robust than with a stimulant drug.…”

“…This measure assessed subjects' preferences for the two study cues (Mayo & de Wit, 2015;Mayo et al, 2013). In this task, subjects viewed each cue (ocean or mountain) combined with images from each of the three computer tasks (from the conditioning sessions).…”

“…Participants underwent a conditioning procedure in which one audiovisual stimulus (cue) was paired with alcohol (ALC; 0.6 g/kg 95% absolute alcohol in juice), and a different cue was paired with a placebo (PBO; 1% absolute alcohol with juice). We measured behavioral preference, self-report ratings, psychophysiological indices of emotional states, and attention for both cues before and after conditioning to assess changes as a function of conditioning (see Mayo & de Wit, 2015). The University of Chicago Biological Science Division Institutional Review Board approved the study.…”

“…The attention measure consisted of a modified visual probe task using the two visual cues (i.e., Mayo & de Wit, 2015;Wardle et al, 2012). During this task, each trial began with a 1-second fixation cross, followed by presentation of the two study cues on the right and left of the screen, for 2 seconds.…”

“…We recently developed a conditioning paradigm showing that healthy, nondependent humans acquire associations between a stimulant drug (methamphetamine; 20 mg) and a contextual, non-drug-related cue (i.e., picture of an ocean or mountain scene) present during the drug-taking experience (Mayo & de Wit, 2015;Mayo et al, 2013). Within this paradigm, we obtained multiple potential indicators of conditioning to determine variation within and across conditioning modalities.…”