Central cholinergic involvement in sequential behavior: Impairments of performance by atropine in a serial multiple choice task for rats

• Two experiments examined atropine effects on rats’ performance of serial patterns.
• Atropine, but not atropine methyl nitrate, impaired serial pattern performance.
• Atropine impaired serial pattern performance dependent on using associative cues.
• Atropine spared rule-based serial pattern performance.

Two experiments examined whether muscarinic cholinergic systems play a role in rats’ ability to perform well-learned highly-structured serial response patterns, particularly focusing on rats’ performance on pattern elements learned by encoding rules versus by acquisition of stimulus–response (S–R) associations. Rats performed serial patterns of responses in a serial multiple choice task in an 8-lever circular array for hypothalamic brain-stimulation reward. Two experiments examined the effects of atropine, a centrally-acting muscarinic cholinergic receptor antagonist, on rats’ ability to perform pattern elements where responses were controlled by rules versus elements, such as rule-inconsistent “violation elements” and elements following “phrasing cues,” where responses were controlled by associative cues. In Experiment 1, 3-element chunks of both patterns were signaled by pauses that served as phrasing cues before chunk-boundary elements, but one pattern also included a violation element that was inconsistent with pattern structure. Once rats reached a high criterion of performance, the drug challenge was intraperitoneal injection of a single dose of 50 mg/kg atropine sulfate. Atropine impaired performance on elements learned by S–R learning, namely, chunk-boundary elements and the violation element, but had no effect on performance of rule-based within-chunk elements. In Experiment 2, patterns were phrased and unphrased perfect patterns (i.e., without violation elements). To control for peripheral effects of atropine, rats were treated with a series of doses of either centrally-acting atropine or peripherally-acting atropine methyl nitrate (AMN), which does not cross the blood–brain barrier. Once rats reached a high criterion, the drug challenges were on alternate days in the order 50, 25, and 100 mg/kg of either atropine sulfate or AMN. Atropine, but not AMN, impaired performance in the phrased perfect pattern for pattern elements where S–R associations were important for performance, namely, chunk-boundary elements. However, in the structurally more ambiguous unphrased perfect pattern where rats had fewer cues and presumably relied more on S–R associations throughout, atropine impaired performance on all pattern elements. Thus, intact muscarinic cholinergic systems were shown to be necessary for discriminative control previously established by S–R learning, but were not necessary for rule-based serial pattern performance.