Squirrel monkeys were trained under fixed-ratio (FR) or fixedinterval (FI) schedules in which the reinforcer was the termination of auditory and visual stimuli associated periodically with the presentation of brief, electric shocks. Methylphenidate, at several doses, exerted selectively different effects upon overall rates of responding engendered by the two types of schedule. The drug suppressed overall rates of responding maintained by FR50 in one monkey and FR250 in another; over the same range of doses, methylphenidate increased the overall rates of responding maintained by a FI schedule in two other animals.
Different local rates of responding were affected differentially since methylphenidate increased the low, near-zero rates of responding observed following a time out under both FR and FI schedules, (the effect being more pronounced for the FI than the FR schedules) but, by contrast, suppressed the higher (terminal) rates of responding preceding a time out (the effect being more pronounced for the FR-than for the FI-controlled performances).
Chronic pretreatment with reserpine (0.3 mg/kg for 10 days), given to two monkeys, progressively reduced the overall rates of responding maintained by the fixed-interval schedule; the rate-suppressive effect of reserpine was antagonized at a dose of 2 mg/kg of methylphenidate in both animals. One monkey, subjected to pretreatment with reserpine, died after an injection of 4 mg/kg methylphenidate; the dosage at 4 mg/kg consistently antagonized the effects of reserpine in the other animal. The resulting pattern of behavior more closely resembled the effects of methylphenidate given alone than control performances recorded in the absence of drug treatment, suggesting that the antagonistic effects of a sympathomimetie amine, such as d-amphetamine, upon reserpine-induced changes in behavior may be a more general phenomenon that can be demonstrated with various rate-enhancing drugs, including methylphenidate.