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Activation of Metabotropic Glutamate Receptor (mGlu2) and Muscarinic Receptors (M1, M4, and M5), Alone or in Combination, and Its Impact on the Acquisition and Retention of Learning in the Morris Water Maze, NMDA Expression and cGMP Synthesis
Abstract
The Morris water maze (MWM) is regarded as one of the most popular tests for detecting spatial memory in rodents. Long-term potentiation and cGMP synthesis seem to be among the crucial factors involved in this type of learning. Muscarinic (M1, M4, and M5 receptors) and metabotropic glutamate (mGlu) receptors are important targets in the search for antipsychotic drugs with the potency to treat cognitive disabilities associated with the disorder. Here, we show that muscarinic receptor activators (VU0357017, VU0152100, and VU0238429) and an mGlu2 receptor activator, LY487379, dose-dependently prevented the development of cognitive disorders as a result of MK-801 administration in the MWM. The dose-ranges of the compounds were as follows: VU0357017, 0.25, 0.5, and 1 mg/kg; VU0152100, 0.05, 0.25, and 1 mg/kg; VU0238429, 1, 5, and 20 mg/kg; and LY487379, 0.5, 3, and 5 mg/kg. The co-administration of LY487379 with each of the individual muscarinic receptor ligands showed no synergistic effect, which contradicts the results obtained earlier in the novel object recognition (NOR) test. MWMlearning resulted in increased cGMP synthesis, both in the cortex and hippocampi, when compared to that in intact animals, which was prevented by MK-801 administration. The investigated compounds at the highest doses reversed this MK-801-induced effect. Neither the procedure nor the treatment resulted in changes in GluN2B-NMDA expression.
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Authors (4)
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Joanna M. Wierońska
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Paulina Cieślik
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Grzegorz Burnat
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Full text
- Publication version
- Accepted or Published Version
- DOI:
- Digital Object Identifier (open in new tab) 10.3390/biom13071064
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- Category:
- Articles
- Type:
- artykuły w czasopismach
- Published in:
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Biomolecules
no. 13,
ISSN: 2218-273X - Language:
- Polish
- Publication year:
- 2023
- Bibliographic description:
- Wierońska J. M., Cieślik P., Burnat G., Kalinowski L.: Activation of Metabotropic Glutamate Receptor (mGlu2) and Muscarinic Receptors (M1, M4, and M5), Alone or in Combination, and Its Impact on the Acquisition and Retention of Learning in the Morris Water Maze, NMDA Expression and cGMP Synthesis// Biomolecules -Vol. 13,iss. 7 (2023), s.1064-
- DOI:
- Digital Object Identifier (open in new tab) 10.3390/biom13071064
- Sources of funding:
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- Narodowe Centrum Nauki, numer grantu 2019/33/B/NZ7/02699 (OPUS 17)
- Verified by:
- Gdańsk University of Technology
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