Dissociation of cholinergic function in spatial and procedural learning in rats

Abstract The cholinergic system has long been known for its role in acquisition and retention of new information. Scopolamine, a muscarinic acetylcholine receptor antagonist impairs multiple memory systems, and this has promoted the notion that drug-induced side effects are responsible for diminishe...

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Bibliographic Details
Published in:Neuroscience 2007-05, Vol.146 (3), p.875-889
Main Authors: von Linstow Roloff, E, Harbaran, D, Micheau, J, Platt, B, Riedel, G
Format: Article
Language:English
Subjects:
acetylcholine
Animals
Biological and medical sciences
Conditioning, Operant - drug effects
Data Interpretation, Statistical
Dose-Response Relationship, Drug
Fundamental and applied biological sciences. Psychology
Learning - drug effects
Learning - physiology
Maze Learning - drug effects
Maze Learning - physiology
Memory - drug effects
Memory - physiology
Memory, Short-Term - drug effects
Memory, Short-Term - physiology
Muscarinic Antagonists - pharmacology
Neurology
Parasympathetic Nervous System - drug effects
Parasympathetic Nervous System - physiology
procedural learning
rat
Rats
Receptors, Muscarinic - physiology
scopolamine
Scopolamine Hydrobromide - pharmacology
Signal Transduction - drug effects
Signal Transduction - physiology
Space Perception - drug effects
Space Perception - physiology
spatial learning water maze
Vertebrates: nervous system and sense organs
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Summary:Abstract The cholinergic system has long been known for its role in acquisition and retention of new information. Scopolamine, a muscarinic acetylcholine receptor antagonist impairs multiple memory systems, and this has promoted the notion that drug-induced side effects are responsible for diminished task execution rather than selective impairments on learning and memory per se. Here, we revisit this issue with the aim to dissociate the effects of scopolamine (0.2–1.0 mg/kg) on spatial learning in the water maze. Experiments 1 and 2 showed that acquisition of a reference memory paradigm with constant platform location is compromised by scopolamine independent of whether the animals are pre-trained or not. Deficits were paralleled by drug induced side-effects on sensorimotor parameters. Experiment 3 explored the role of muscarinic receptors in acquisition of an episodic-like spatial delayed matching to position (DMTP) protocol, and scopolamine still caused a learning deficit and side-effects on sensorimotor performance. Rats extensively pre-trained in the DMTP protocol with 30 s and 1 h delays over several months in experiment 4 and tested in a within-subject design under saline and scopolamine had no sensorimotor deficits, but spatial working memory remained compromised. Experiment 5 used the rising Atlantis platform in the DMTP paradigm. Intricate analysis of the amount of dwelling and its location revealed a clear deficit in spatial working memory induced by scopolamine, but there was no effect on sensorimotor or procedural task demands. Apart from the well-known contribution to sensorimotor and procedural learning, our findings provide compelling evidence for an important role of muscarinic acetylcholine receptor signaling in spatial episodic-like memory.
ISSN:0306-4522
1873-7544
DOI:10.1016/j.neuroscience.2007.02.038