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  Attenuation of novelty-induced hyperactivity of gria1-/- mice by cannabidiol and hippocampal inhibitory chemogenetics

Aitta-aho, T., Maksimovic, M., Dahl, K., Sprengel, R., & Korpi, E. R. (2019). Attenuation of novelty-induced hyperactivity of gria1-/- mice by cannabidiol and hippocampal inhibitory chemogenetics. Frontiers in pharmacology, 309, pp. 1-11. doi:10.3389/fphar.2019.00309.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0003-A09D-7 Version Permalink: http://hdl.handle.net/21.11116/0000-0003-A09E-6
Genre: Journal Article

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 Creators:
Aitta-aho, Teemu, Author
Maksimovic, Milica, Author
Dahl, Kristiina, Author
Sprengel, Rolf1, 2, 3, Author              
Korpi, Esa R., Author
Affiliations:
1Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Max Planck Society, ou_1497704              
2Olfaction Web, Max Planck Institute for Medical Research, Max Planck Society, ou_1497733              
3Rolf Sprengel Group, Max Planck Institute for Medical Research, Max Planck Society, ou_1497741              

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Free keywords: AMPA receptors; DREADD; c-Fos; cannabidiol; hM4Gi; hippocampus; hyperactivity; novelty
 Abstract: Gene-targeted mice with deficient AMPA receptor GluA1 subunits (Gria1-/- mice) show robust hyperlocomotion in a novel environment, suggesting them to constitute a model for hyperactivity disorders such as mania, schizophrenia and attention deficit hyperactivity disorder. This behavioral alteration has been associated with increased neuronal activation in the hippocampus, and it can be attenuated by chronic treatment with antimanic drugs, such as lithium, valproic acid, and lamotrigine. Now we found that systemic cannabidiol strongly blunted the hyperactivity and the hippocampal c-Fos expression of the Gria1-/- mice, while not affecting the wild-type littermate controls. Acute bilateral intra-dorsal hippocampal infusion of cannabidiol partially blocked the hyperactivity of the Gria1-/- mice, but had no effect on wild-types. The activation of the inhibitory DREADD receptor hM4Gi in the dorsal hippocampus by clozapine-N-oxide robustly inhibited the hyperactivity of the Gria1-/- mice, but had no effect on the locomotion of wild-type mice. Our results show that enhanced neuronal excitability in the hippocampus is associated with pronounced novelty-induced hyperactivity of GluA1 subunit-deficient mice. When this enhanced response of hippocampal neurons to novel stimuli is specifically reduced in the hippocampus by pharmacological treatment or by chemogenetic inhibition, Gria1-/- mice recover from behavioral hyperactivity, suggesting a hippocampal dysfunction in hyperactive behaviors that can be treated with cannabidiol.

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Language(s): eng - English
 Dates: 2018-12-132019-09-132019-03-29
 Publication Status: Published in print
 Pages: 11
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 Table of Contents: -
 Rev. Method: Peer
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Title: Frontiers in pharmacology
Source Genre: Journal
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Publ. Info: Lausanne : Frontiers Media
Pages: - Volume / Issue: - Sequence Number: 309 Start / End Page: 1 - 11 Identifier: ISSN: 1663-9812