Targeting the cannabinoid receptor CB2 in a mouse model of l-dopa induced dyskinesia.

Rentsch, P; Stayte, S; Egan, T; Clark, I; Vissel, B

Targeting the cannabinoid receptor CB2 in a mouse model of l-dopa induced dyskinesia.

Rentsch, P

Stayte, S

Egan, T Clark, I Vissel, B

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Publisher:: Elsevier
Publication Type:: Journal Article
Citation:: Neurobiology of Disease, 2020, 134, pp. 104646-104646
Issue Date:: 2020-02

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Field	Value	Language
dc.contributor.author	Rentsch, P https://orcid.org/0000-0002-2108-3568
dc.contributor.author	Stayte, S https://orcid.org/0000-0002-6518-1979
dc.contributor.author	Egan, T
dc.contributor.author	Clark, I
dc.contributor.author	Vissel, B https://orcid.org/0000-0001-8860-8050
dc.date.accessioned	2020-10-21T05:15:01Z
dc.date.available	2021-01-28T18:06:18Z
dc.date.issued	2020-02
dc.identifier.citation	Neurobiology of Disease, 2020, 134, pp. 104646-104646
dc.identifier.issn	0969-9961
dc.identifier.issn	1095-953X
dc.identifier.uri	http://hdl.handle.net/10453/143433
dc.description.abstract	L-dopa induced dyskinesia (LID) is a debilitating side-effect of the primary treatment used in Parkinson's disease (PD), l-dopa. Here we investigate the effect of HU-308, a cannabinoid CB2 receptor agonist, on LIDs. Utilizing a mouse model of PD and LIDs, induced by 6-OHDA and subsequent l-dopa treatment, we show that HU-308 reduced LIDs as effectively as amantadine, the current frontline treatment. Furthermore, treatment with HU-308 plus amantadine resulted in a greater anti-dyskinetic effect than maximally achieved with HU-308 alone, potentially suggesting a synergistic effect of these two treatments. Lastly, we demonstrated that treatment with HU-308 and amantadine either alone, or in combination, decreased striatal neuroinflammation, a mechanism which has been suggested to contribute to LIDs. Taken together, our results suggest pharmacological treatments with CB2 agonists merit further investigation as therapies for LIDs in PD patients. Furthermore, since CB2 receptors are thought to be primarily expressed on, and signal through, glia, our data provide weight to suggestion that neuroinflammation, or more specifically, altered glial function, plays a role in development of LIDs.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	Elsevier
dc.relation.ispartof	Neurobiology of Disease
dc.relation.isbasedon	10.1016/j.nbd.2019.104646
dc.rights	Elsevier required licence: © 2020 . This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/. The definitive publisher version is available online at https://doi.org/10.1016/j.nbd.2019.104646	en_US
dc.rights	info:eu-repo/semantics/embargoedAccess
dc.subject	1103 Clinical Sciences, 1109 Neurosciences
dc.subject.classification	Neurology & Neurosurgery
dc.title	Targeting the cannabinoid receptor CB2 in a mouse model of l-dopa induced dyskinesia.
dc.type	Journal Article
utslib.citation.volume	134
utslib.location.activity	United States
utslib.for	1103 Clinical Sciences
utslib.for	1109 Neurosciences
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney
utslib.copyright.status	open_access	*
pubs.consider-herdc	true
dc.date.updated	2020-10-21T05:14:43Z
pubs.publication-status	Published
pubs.volume	134

Abstract:

L-dopa induced dyskinesia (LID) is a debilitating side-effect of the primary treatment used in Parkinson's disease (PD), l-dopa. Here we investigate the effect of HU-308, a cannabinoid CB2 receptor agonist, on LIDs. Utilizing a mouse model of PD and LIDs, induced by 6-OHDA and subsequent l-dopa treatment, we show that HU-308 reduced LIDs as effectively as amantadine, the current frontline treatment. Furthermore, treatment with HU-308 plus amantadine resulted in a greater anti-dyskinetic effect than maximally achieved with HU-308 alone, potentially suggesting a synergistic effect of these two treatments. Lastly, we demonstrated that treatment with HU-308 and amantadine either alone, or in combination, decreased striatal neuroinflammation, a mechanism which has been suggested to contribute to LIDs. Taken together, our results suggest pharmacological treatments with CB2 agonists merit further investigation as therapies for LIDs in PD patients. Furthermore, since CB2 receptors are thought to be primarily expressed on, and signal through, glia, our data provide weight to suggestion that neuroinflammation, or more specifically, altered glial function, plays a role in development of LIDs.

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http://hdl.handle.net/10453/143433