Rationale: Although the behavioral, subjective, and physiological effects of oral cocaine have been investigated, its reinforcing effects have not been demonstrated. Objective: The primary aims of this study were to examine the reinforcing effects of oral cocaine and determine whether such effects can be influenced by manipulating behavioral requirements following drug ingestion. Methods: Nine adult volunteers with histories of cocaine abuse were trained to discriminate between orally administered cocaine (100 mg/70 kg) and placebo capsules under double-blind conditions. Following acquisition of cocaine vs placebo discrimination (80% correct), the reinforcing effects of cocaine were determined using two different choice conditions (dependent and independent). Volunteers were first exposed to cocaine and placebo once each with a relaxation activity (sitting in a cushioned chair) and a vigilance activity (performing a computer task). Following exposure to each drug with each activity, volunteers began the dependent choice condition. Every 2 days volunteers chose which drug (cocaine or placebo) they ingested with the vigilance and relaxation activities. Volunteers could not choose the same drug with both activities. This procedure occurred 5 times over a 10-day period. The independent choice condition took place over 2 days. On one day, volunteers chose which drug (cocaine or placebo) they ingested with the relaxation activity and, on the other day (in counterbalanced order), which drug they ingested with the vigilance activity. Volunteers were allowed to select the same drug with both activities. Results: All volunteers successfully acquired the cocaine vs placebo discrimination. In the dependent choice condition, all volunteers significantly chose cocaine over placebo with the vigilance activity and chose placebo over cocaine with the relaxation activity. In the independent choice condition, volunteers significantly chose cocaine over placebo with the vigilance activity (i.e., cocaine functioned as a positive reinforcer in the vigilance context). Interestingly, the independent choice condition also showed that volunteers chose placebo over cocaine with the relaxation activity (i.e,,cocaine functioned as a negative reinforcer because it was avoided relative to placebo). Conclusion: The study shows that the behavioral requirements following drug ingestion can be a determinant of whether or not oral cocaine functions as a reinforcer in volunteers with histories of cocaine abuse
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