Reinforcing effects of oral cocaine: contextual determinants

Rationale: Although the behavioral, subjective, and physiological effects o f oral cocaine have been investigated, its reinforcing effects have not bee n demonstrated. Objective: The primary aims of this study were to examine t he reinforcing effects of oral cocaine and determine whether such effects c an be influenced by manipulating behavioral requirements following drug ing estion. 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 (dependen t and independent). Volunteers were first exposed to cocaine and placebo on ce each with a relaxation activity (sitting in a cushioned chair) and a vig ilance activity (performing a computer task). Following exposure to each dr ug with each activity, volunteers began the dependent choice condition. Eve ry 2 days volunteers chose which drug (cocaine or placebo) they ingested wi th 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 t he relaxation activity and, on the other day (in counterbalanced order), wh ich drug they ingested with the vigilance activity. Volunteers were allowed to select the same drug with both activities. Results: All volunteers succ essfully acquired the cocaine vs placebo discrimination. In the dependent c hoice condition, all volunteers significantly chose cocaine over placebo wi th the vigilance activity and chose placebo over cocaine with the relaxatio n activity. In the independent choice condition, volunteers significantly c hose cocaine over placebo with the vigilance activity (i.e., cocaine functi oned as a positive reinforcer in the vigilance context). Interestingly, the independent choice condition also showed that volunteers chose placebo ove r cocaine with the relaxation activity (i.e,,cocaine functioned as a negati ve reinforcer because it was avoided relative to placebo). Conclusion: The study shows that the behavioral requirements following drug ingestion can b e a determinant of whether or not oral cocaine functions as a reinforcer in volunteers with histories of cocaine abuse.