Reinforcing and subjective effects of morphine in human opioid abusers: effect of dose and alternative reinforcer

Rationale: Although most opioid self-administration research has been condu cted with laboratory animals, such research with humans is necessary to ans wer questions unique to human drug-taking behavior. Objective: We investiga ted the influence of morphine dose and an alternative non-drug reinforcer a n choice between morphine versus money and examined the relationship betwee n drug-reinforced behavior and subjective euphoria. Methods: Five male opio id users participated in the 7-week study. During the first 5 weeks, a sing le dose of morphine (0, 4, 8, 16, or 32 mg/70 kg) was available each week. On Monday, subjects received an IM injection of the dose tested that week. On Tuesday, Thursday, and Friday, subjects could work for morphine or money under a second-order, progressive ratio schedule. For each primary ratio c ompleted on the drug lever, subjects earned one-ninth of the available drug dose, and for each ratio completed on the money lever, subjects earned $1. Total amount of drug earned was administered in a single WI injection at t he end of the session; money earned was credited to the subject's account. Results: As morphine dose increased, responding for drug increased in an or derly manner and responding for money decreased. During the final phase of the study, the lowest and highest doses that maintained drug responding for each subject were repeated, and the value of the alternative reinforcer wa s increased to $2 per ratio. This manipulation was associated with decrease d drug-maintained responding at the lowest, but not the highest, reinforcin g dose of morphine. Conclusion: The progressive ratio, concurrent access pr ocedure may be useful in predicting the outcome of drug abuse treatment int erventions that use alternate reinforcement strategies.