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

Abstract

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.

Concurrent cognitive processes in rat serial pattern learning: II. Discrimination learning, rule learning, chunk length, and multiple-item memories

“…MK-801 interferes with learning to anticipate chunkboundary elements and the violation element with virtually no disruption of acquisition of within-chunk elements (Fountain & Rowan, 2000). Similar results are obtained with acute exposures of muscarinic cholinergic antagonists such as atropine (Chenoweth & Fountain, 2015;Fountain, Rowan, & Wollan, 2013).…”

Serial pattern learning in pigeons: Rule-based or associative?

“…Dissociations in learning and performance consistent with the foregoing behavioral and cognitive distinctions have been observed in rats following acute systemic treatment with MK-801, an N-methyl-D-aspartate receptor (NMDAr) antagonist, and with atropine, a muscarinic cholinergic antagonist (Chenoweth & Fountain, 2015; Fountain & Rowan, 2000; Fountain, Rowan, & Wollan, 2013). Similar dissociations have also been observed in adolescent nicotine effects on adult learning (Fountain et al, 2008; Pickens et al, 2013).…”

Paradoxical effects of injection stress and nicotine exposure experienced during adolescence on learning in a serial multiple choice (SMC) task in adult female rats

“…Since the different pattern element types are learned using distinct cognitive mechanisms, it is not surprising to find that the same drug or toxic agent can result in differential facilitation of learning, impairment of learning, and no effect on learning for different element types in individual rats in the SMC task. Dissociations in learning and performance consistent with the foregoing behavioral and cognitive distinctions have been observed in rats following acute systemic treatment with MK-801, an N-methyl-D-aspartate receptor (NMDAr) antagonist, and with atropine, a muscarinic cholinergic antagonist (Fountain & Rowan, 2000; Fountain, Rowan, & Wollan, 2013). …”