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Distinctive Effects of D1 and D2 Receptor Agonists on Cortico-Basal Ganglia Oscillations in a Rodent Model of L-DOPA-Induced Dyskinesia

Skovgård, Katrine LU ; Barrientos, Sebastian A. LU orcid ; Petersson, Per LU ; Halje, Pär LU and Cenci, M. Angela LU orcid (2023) In Neurotherapeutics 20(1). p.304-324
Abstract

L-DOPA-induced dyskinesia (LID) in Parkinson’s disease has been linked to oscillatory neuronal activities in the cortico-basal ganglia network. We set out to examine the pattern of cortico-basal ganglia oscillations induced by selective agonists of D1 and D2 receptors in a rat model of LID. Local field potentials were recorded in freely moving rats using large-scale electrodes targeting three motor cortical regions, dorsomedial and dorsolateral striatum, external globus pallidus, and substantial nigra pars reticulata. Abnormal involuntary movements were elicited by the D1 agonist SKF82958 or the D2 agonist sumanirole, while overall motor activity was quantified using video analysis (DeepLabCut). Both SKF82958 and sumanirole induced... (More)

L-DOPA-induced dyskinesia (LID) in Parkinson’s disease has been linked to oscillatory neuronal activities in the cortico-basal ganglia network. We set out to examine the pattern of cortico-basal ganglia oscillations induced by selective agonists of D1 and D2 receptors in a rat model of LID. Local field potentials were recorded in freely moving rats using large-scale electrodes targeting three motor cortical regions, dorsomedial and dorsolateral striatum, external globus pallidus, and substantial nigra pars reticulata. Abnormal involuntary movements were elicited by the D1 agonist SKF82958 or the D2 agonist sumanirole, while overall motor activity was quantified using video analysis (DeepLabCut). Both SKF82958 and sumanirole induced dyskinesia, although with significant differences in temporal course, overall severity, and body distribution. The D1 agonist induced prominent narrowband oscillations in the high gamma range (70–110 Hz) in all recorded structures except for the nigra reticulata. Additionally, the D1 agonist induced strong functional connectivity between the recorded structures and the phase analysis revealed that the primary motor cortex (forelimb area) was leading a supplementary motor area and striatum. Following treatment with the D2 agonist, narrowband gamma oscillations were detected only in forelimb motor cortex and dorsolateral striatum, while prominent oscillations in the theta band occurred in the globus pallidus and nigra reticulata. Our results reveal that the dyskinetic effects of D1 and D2 receptor agonists are associated with distinct patterns of cortico-basal ganglia oscillations, suggesting a recruitment of partially distinct networks.

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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Basal ganglia, Dopamine agonist, Dyskinesia, Local field potential, Oscillations, Parkinson’s disease
in
Neurotherapeutics
volume
20
issue
1
pages
304 - 324
publisher
Springer
external identifiers
  • scopus:85141529838
  • pmid:36344723
ISSN
1933-7213
DOI
10.1007/s13311-022-01309-5
project
Models and biomarkers of motor and neuropsychiatric complications in Parkinson’s disease
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2022, The Author(s).
id
fef30b02-a279-4c18-9314-0eb510b9896e
date added to LUP
2022-12-07 20:15:49
date last changed
2024-04-16 05:02:36
@article{fef30b02-a279-4c18-9314-0eb510b9896e,
  abstract     = {{<p>L-DOPA-induced dyskinesia (LID) in Parkinson’s disease has been linked to oscillatory neuronal activities in the cortico-basal ganglia network. We set out to examine the pattern of cortico-basal ganglia oscillations induced by selective agonists of D1 and D2 receptors in a rat model of LID. Local field potentials were recorded in freely moving rats using large-scale electrodes targeting three motor cortical regions, dorsomedial and dorsolateral striatum, external globus pallidus, and substantial nigra pars reticulata. Abnormal involuntary movements were elicited by the D1 agonist SKF82958 or the D2 agonist sumanirole, while overall motor activity was quantified using video analysis (DeepLabCut). Both SKF82958 and sumanirole induced dyskinesia, although with significant differences in temporal course, overall severity, and body distribution. The D1 agonist induced prominent narrowband oscillations in the high gamma range (70–110 Hz) in all recorded structures except for the nigra reticulata. Additionally, the D1 agonist induced strong functional connectivity between the recorded structures and the phase analysis revealed that the primary motor cortex (forelimb area) was leading a supplementary motor area and striatum. Following treatment with the D2 agonist, narrowband gamma oscillations were detected only in forelimb motor cortex and dorsolateral striatum, while prominent oscillations in the theta band occurred in the globus pallidus and nigra reticulata. Our results reveal that the dyskinetic effects of D1 and D2 receptor agonists are associated with distinct patterns of cortico-basal ganglia oscillations, suggesting a recruitment of partially distinct networks.</p>}},
  author       = {{Skovgård, Katrine and Barrientos, Sebastian A. and Petersson, Per and Halje, Pär and Cenci, M. Angela}},
  issn         = {{1933-7213}},
  keywords     = {{Basal ganglia; Dopamine agonist; Dyskinesia; Local field potential; Oscillations; Parkinson’s disease}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{304--324}},
  publisher    = {{Springer}},
  series       = {{Neurotherapeutics}},
  title        = {{Distinctive Effects of D1 and D2 Receptor Agonists on Cortico-Basal Ganglia Oscillations in a Rodent Model of L-DOPA-Induced Dyskinesia}},
  url          = {{http://dx.doi.org/10.1007/s13311-022-01309-5}},
  doi          = {{10.1007/s13311-022-01309-5}},
  volume       = {{20}},
  year         = {{2023}},
}