Random-ratio schedules produce greater demand for i.v. drug administration than fixed-ratio schedules in rhesus monkeys

Rationale Organisms emit more responses when food is provided according to random as compared with fixed schedules of reinforcement. Similarly, many human behaviors deemed compulsive are maintained on variable schedules (e.g., gambling). If greater amounts of behavior are maintained by drugs of abuse when earned according to variably reinforced schedules, this would suggest that excessive drug-taking behavior may be due in part to the nature of drug availability. Objectives The aim was to determine whether random schedules of contingent intravenous drug delivery would produce more responding than similarly priced fixed schedules. Methods Six rhesus macaque subjects responded to produce cocaine (0.003–0.03 mg/kg/inj), remifentanil (0.01–1.0 μg/kg/inj), or ketamine (0.01–0.1 mg/kg/inj) according to either fixed or random ratio requirements that increased systematically across sessions. Demand curves were generated with the most effective dose of each drug and compared across drug and schedule type. Results Cocaine and remifentanil maintained higher levels and rates of responding when earned according to random-ratio schedules as compared with fixed-ratio schedules. This difference was most pronounced when drugs were available at high unit prices. Differences in responding across the schedule types generated by ketamine—a lesser-valued reinforcer—were qualitatively similar but smaller in magnitude. Conclusions The current study provides a systematic replication across reinforcer type demonstrating that drugs delivered after a random number of responses generate more behavior than those delivered according to a fixed schedule. The variable nature of the availability of drugs of abuse—particularly those that are scarce or expensive—may be a contributing factor to excessive drug intake by humans. This effect is most likely to be observed when more highly demanded (reinforcing) drugs are being consumed.