The Effects of Expectation on Natural and Drug -Induced Rewards

Overview

Background: * Environmental cues frequently induce expectancies in individuals that may strongly influence the actual experience associated with the cue. This has both positive and negative consequences for behavior and decision making. For instance, when an addicted individual experiences cues associated with imminent drug taking, an expectancy of the coming experience is also formed and very likely has an effect on the subsequent experience of the drug. * Researchers are interested in studying how the brain responds to these kinds of environmental cues and expectancies in order to learn more about addiction and craving in substance-abusing individuals. Objectives: * To compare the response to rewards (both drug-related and non-drug-related) in cocaine users and non-using individuals. * To study the effect of expectation on reward-related (both drug-induced and non-drug-induced) responses and brain activity in cocaine users and non-using individuals. Eligibility: -Individuals between 18 and 45 years of age who are regular cocaine users but otherwise healthy, or healthy individuals who are not cocaine users. Design: * This study involves two experiments. Participants will be assigned to one or both experiments. * Participants must not use any drugs for at least 3 days before the visit, may not consume alcohol for 24 hours before the visit, and may not consume caffeinated beverages for 12 hours before the visit. On the day of the visit, participants will provide both urine and breath samples to test for drug/alcohol use. * Experiment 1: In the MRI scanner, participants will respond to questions and images on a screen, and will receive small amounts of flavored liquid (chocolate or cherry) through a tube in the mouth. * Experiment 2: In the MRI scanner, participants will respond to questions and images on a screen, and will receive injections of liquid (saline solution or a drug that provides a high similar to cocaine) through an intravenous line. Participants in this experiment will return for follow-up visits and provide urine samples for further study. * The specific assignment (to Experiment 1 or Experiment 2 or both experiments) will determine the number of study days and follow-up visits required.

Objective: Environmental cues frequently induce expectancies in the course of normal daily life. When an individual smells and sees the coffee before tasting it, an expectancy of the coming experience is formed that influences the actual experience of consuming the coffee. Similarly, when an addicted individual experiences cues associated with imminent drug taking, an expectancy of the coming experience is also formed. This protocol will examine neural responses to cues predictive of a stimulus (neutral or rewarding) and to the subsequent receipt of the predicted stimulus. Study Population: Study participants will include 18-50 year old, male and non-pregnant female otherwise healthy cocaine dependent individuals and control individuals who have a history of some stimulant use but no history of abuse or dependence on any other drug other than nicotine. Design: The study will employ fMRI to elucidate the neural underpinnings of reward processing. The rewarding stimuli to be studied will be taste stimuli (small squirt of juice or chocolate) and a drug stimulus (intravenous methylphenidate (IV MPH)). For taste stimuli, cues will vary in sensory modality (visual vs. olfactory) and in novelty (well-known vs. novel). Novel and well-known cue stimuli will be included on each experimental day so the development of expectancy can be studied as the cue-taste pairing is learned and compared to the well-known cue-taste pairing. The MPH/saline injections will receive a written cue. Outcome Measures: BOLD fMRI signal to reward stimuli will be compared in the various cuing conditions.