Effects of atropine on the repeated acquisition and performance of response sequences in humans.

The present study assessed a 24-hr time course for the acute effects of intramuscular injections of atropine sulfate (0, 1.5, 3.0, and 6.0 mg/70 kg) in healthy adult humans responding under a two-component multiple schedule of repeated acquisition and performance of response sequences. Subjects resided in an inpatient research ward for the duration of the study. In each component of the multiple schedule, subjects completed a different sequence of 10 responses in a predetermined order using three keys of a numeric keypad. In the acquisition component, the subjects' task was to acquire a new sequence each session. Eight sessions were conducted daily: one immediately before administration of the drug and then 0.5, 1.5, 3.0, 5.0, 7.0, 9.0, and 24.0 hr after administration. In the performance component, the response sequence always remained the same. Overall percentage of errors increased and overall response rates decreased in the acquisition and performance components as an orderly function of drug dose. However, these effects were selective in that behavior in the acquisition component generally was affected at lower doses than in the performance component. When behavior was affected in both the acquisition and performance components, the time courses of effects were similar. Drug effects began at 0.5 or 1.5 hr, reached peak effects between 3.0 and 5.0 hr, and returned to placebo levels between 7.0 and 9.0 hr postdrug in both schedule components. None of the drug doses produced reliable effects the day after drug administration (24-hr postdrug) in either schedule component. The present study provides the first within-subject assessment of the magnitude and duration of the effects of an anticholinergic on repeated acquisition and performance baselines and extends to atropine the selective effects on these two baselines demonstrated previously with other compounds in humans and nonhumans.