Drug Effects on Preference and Reward
Condition: Drug Addiction
MeSH terms: Substance-Related Disorders
Study type: Observational

Summary: 
      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.
    

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.
    

Intervention name(s): Pairing condition; Pairing condition
Intervention type(s): Behavioral; Behavioral
Intervention description(s): 20 mg methamphetamine or placebo on four 4-hour laboratory sessions
Other intervention name(s): Paired, unpaired; Low, high or no reward
Observational model: Case-Only
Sampling method: Probability Sample
Study population: 
        healthy adults
      
Keywords: methamphetamine; subjective; conditioning; preference