Document Type
Article
Publication Date
12-1-2018
Journal
Psychopharmacology
Volume
235
Issue
12
First Page
3495
Last Page
3508
URL with Digital Object Identifier
10.1007/s00213-018-5065-7
Abstract
© 2018, The Author(s). Rationale: Muscarinic acetylcholine receptors are known to play key roles in mediating cognitive processes, and impaired muscarinic cholinergic neurotransmission is associated with normal ageing processes and Alzheimer’s disease. However, the specific contributions of the individual muscarinic receptor subtypes (M1–M5) to cognition are presently not well understood. Objectives: The aim of this study was to investigate the contribution of M2-type muscarinic receptor signalling to sustained attention, executive control and learning and memory. Methods: M2 receptor-deficient (M2−/−) mice were tested on a touchscreen-operated task battery testing visual discrimination, behavioural flexibility, object-location associative learning, attention and response control. Spontaneous recognition memory for real-world objects was also assessed. Results: We found that M2−/− mice showed an enhancement of attentional performance, but significant deficits on some tests of learning and memory. Executive control and visual discrimination were unaffected by M2-depletion. Conclusions: These findings suggest that M2 activation has heterogeneous effects across cognitive domains, and provide insights into how acetylcholine may support multiple specific cognitive processes through functionally distinct cholinergic receptor subtypes. They also suggest that therapeutics involving M2 receptor-active compounds should be assessed across a broad range of cognitive domains, as they may enhance some cognitive functions, but impair others.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Notes
Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
The publisher's version can be found at:
Romberg, C., Bartko, S., Wess, J. et al. Impaired object-location learning and recognition memory but enhanced sustained attention in M2 muscarinic receptor-deficient mice. Psychopharmacology 235, 3495–3508 (2018). https://doi.org/10.1007/s00213-018-5065-7