Drug Effects on Preference and Reward

Classical conditioning is widely used to study motivational properties of addictive drugs in animals, but has rarely been used in humans. Here, we are establishing a procedure suitable for studying the neurobiology and individual determinants of classical conditioning in humans. Healthy volunteers are 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 perform tasks known to activate the ventral striatum in fMRI studies. The tasks are performed in the presence of a distinctive context, consisting of a screen background image of a beach or of mountains, accompanied by corresponding sounds. Separate groups of subjects carry out the tasks under high or low reward conditions. Within each of the two reward conditions, one group (paired), receives methamphetamine (20 mg, oral) or placebo consistently associated with one of the contexts, while the other (unpaired) receives drug or placebo unrelated to context. A fifth group (paired) perform the tasks with contextual cues but in the absence of monetary incentives. Before and after conditioning, participants carry out a series of forced choice tasks, and change of preference over time was analyzed.

Study Overview

• Status: Completed
• Conditions: Drug Addiction
• Intervention / Treatment: Behavioral: Pairing condition; Behavioral: Pairing condition

Detailed Description

Subjects are assigned to one of 5 groups: Paired, high reward (PairHi; n=24); Paired, low reward (PairLo; n=24); Paired no reward (PairNone; n=23); Unpaired, high reward (UnpHi; n=7); and Unpaired, low-reward (UnpLo; n=9). Each participant attends an orientation session, followed by four 4h conditioning sessions separated by at least 48h, and a 2h test session. During the initial orientation session, subjects practice the computer tasks together with the environmental stimuli to be paired during the conditioning sessions, and carry out a series of choices for the tasks and images (see below). All subjects receive methamphetamine (20 mg) on two conditioning sessions and placebo on the other two sessions, administered under double-blind conditions. Subjects differ in whether environmental stimuli are consistently paired with the drug administration. The three paired groups consistently receive drug and placebo in combination with one of the two sets of visual and auditory background stimuli (see below). The two unpaired groups receive each treatment in combination with one of the stimuli sets on one session, and the other on the other.

During all four conditioning sessions, subjects perform a series of computer tasks. Depending on group assignment, subjects are able to earn high ( PairHi, UnpHi) or low monetary reward ( PairLo, UnpLo), but this is not contingent on subjects' performance. Each run for each game begins with a credit to prevent a negative outcome early in the run. The PairNone group play the same games without monetary reward. The order of the three games and the background images used are randomized across subjects, but remain constant within subjects.

Tasks are presented in the presence of the two distinctive compound stimuli consisting of a background screen visible behind the task presentation and accompanied by a corresponding sound. One set of stimuli depicts a summer beach view accompanied by the sound of ocean waves. The other depicts summer alpine scenery accompanied by birdsong.

The primary outcome measure is the change in preference ratings for the study stimuli, from before to after conditioning. This is a behavioral study, designed to develop a novel procedure for future imaging studies.

• Study Type: Observational
• Enrollment (Actual): 103

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

healthy adults

Description

Inclusion Criteria:

• 18-35, good healthy, normal weight, high school education, normal electrocardiogram, no psychiatric disorders,

Exclusion Criteria:

• current medications, night shift work, abnormal electrocardiogram, medical problems

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Pairing group; Paired, high reward, oral methamphetamine (20 mg) vs placebo Paired, low reward, oral methamphetamine (20 mg) vs placebo Paired, no reward, oral methamphetamine (20 mg) vs placebo Unpaired, oral methamphetamine (20 mg) vs placebo	Behavioral: Pairing condition; Behavioral: Pairing condition; 20 mg methamphetamine or placebo on four 4-hour laboratory sessions; Other Names: Paired, unpaired; Low, high or no reward

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Preference for paired stimulus	Subjects rate their preference for several pairs of stimuli before and after conditioning pairings. The stimuli are presented on a computer screen in the pre and post preference tests, and the change in preference after the conditioning trials is the primary outcome measure.	2-3 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subjective responses to methamphetamine	Subjects complete standardized mood questionnaires after receiving methamphetamine or placebo on each of the four conditioning trials. Blood pressure and heart rate are also measured at these times.	2-3 weeks

Collaborators and Investigators

• Sponsor: University of Chicago
• Collaborators: National Institute on Drug Abuse (NIDA); National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Study record dates

Study Major Dates

• Study Start: December 1, 2010
• Primary Completion (Actual): July 1, 2012
• Study Completion (Actual): July 1, 2012

Study Registration Dates

• First Submitted: October 29, 2012
• First Submitted That Met QC Criteria: November 2, 2012
• First Posted (Estimate): November 6, 2012

Study Record Updates

• Last Update Posted (Estimate): September 5, 2013
• Last Update Submitted That Met QC Criteria: September 4, 2013
• Last Verified: November 1, 2012

More Information

Terms related to this study

• Keywords: methamphetamine; subjective; conditioning; preference
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders
• Other Study ID Numbers: 10-618A; R01DA002812 (U.S. NIH Grant/Contract); HHSN275201100328P (Other Identifier: NIAAA)