Reinforcing and subject-rated effects of methylphenidate and d-amphetamine in non-drug-abusing humans.

Abstract

The reinforcing effects of methylphenidate (20-40 mg), d-amphetamine (10-20 mg), and placebo were assessed in eight healthy, non-sleep-deprived, non-drug-abusing outpatient volunteers. A modified progressive-ratio schedule was used to assess drug reinforcement in which a sampling session always preceded a self-administration session. During sampling sessions, volunteers received a drug dose to acquaint them with the drug effects. Drug doses were administered in eight identical capsules (i.e., each capsule contained 12.5% of the total dose). During self-administration sessions, which generally were conducted the next day, volunteers were given eight opportunities to work on a computer and could earn all, or some, of the capsules that were administered the previous day. To earn the first capsule, volunteers had to click a computer mouse 50 times. The number of clicks required to earn each additional capsule doubled (i.e., 100, 200, 400, 800, 1,600, 3,200, and 6,400 clicks). The dependent measure on this task was the break point (i.e., the last ratio completed). To characterize more fully the behavioral effects of methylphenidate and d-amphetamine, a battery of subject-rated drug-effect questionnaires, performance tasks, and physiologic measures was also used. Both doses of d-amphetamine increased the break point significantly above placebo levels, whereas only the high dose of methylphenidate did so. Break-point values for the doses of methylphenidate and d-amphetamine that maintained the greatest responding did not differ significantly. Methylphenidate and d-amphetamine produced some stimulantlike subject-rated drug effects (e.g., increased ratings of "drug liking"). These data suggest that methylphenidate, like d-amphetamine, can function as a reinforcer under a modified progressive-ratio schedule and, by inference, has at least some abuse potential in healthy, non-sleep-deprived, non-drug-abusing volunteers.