Alternating lever cyclic-ratio schedule analysis of the effects of atropine sulfate

Cholinergic dysfunction has been implicated in the behavioral and memory impairment that is the hallmark of conditions such as delirium and Alzheimer's Disease. Anticholinergic drugs have been widely used in procedures designed to mimic aspects of the pathology of these conditions in rats. Procedures in use vary widely in sensitivity and behavioral specificity and may be confounded by administration of high drug doses that may not be physiologically relevant. The current study proposes the use of rats responding on an alternating lever cyclic-ratio schedule to study the effects of the anticholinergic compound atropine sulfate. This procedure enables simultaneous measurement of anticipatory ratio tracking (postreinforcement pause durations), perseverations (lever switching errors), and nonspecific peripheral drug effects (running response rates). Results of this study suggest that the schedule is sensitive to low drug doses (0.1-1.0 mg/kg atropine), measures the ability to track changing ratio conditions and to execute lever alternation, and allows for monitoring of peripheral drug effects during behavioral testing. The procedure's sensitivity and low effective dose range may make it useful in the study of behaviors related to anticholinergic effects.