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Neurophysiological effects in cortico-basal ganglia-thalamic circuits of antidyskinetic treatment with 5-HT1A receptor biased agonists

Brys, Ivani LU ; Halje, Pär LU ; Scheffer-Teixeira, Robson; Varney, Mark; Newman-Tancredi, Adrian and Petersson, Per LU (2018) In Experimental Neurology 302. p.155-168
Abstract

Recently, the biased and highly selective 5-HT1A agonists, NLX-112, F13714 and F15599, have been shown to alleviate dyskinesia in rodent and primate models of Parkinson's disease, while marginally interfering with antiparkinsonian effects of levodopa. To provide more detailed information on the processes underlying the alleviation of dyskinesia, we have here investigated changes in the spectral contents of local field potentials in cortico-basal ganglia-thalamic circuits following treatment with this novel group of 5-HT1A agonists or the prototypical agonist, 8-OH-DPAT. Dyskinetic symptoms were consistently associated with 80 Hz oscillations, which were efficaciously suppressed by all 5-HT1A agonists and... (More)

Recently, the biased and highly selective 5-HT1A agonists, NLX-112, F13714 and F15599, have been shown to alleviate dyskinesia in rodent and primate models of Parkinson's disease, while marginally interfering with antiparkinsonian effects of levodopa. To provide more detailed information on the processes underlying the alleviation of dyskinesia, we have here investigated changes in the spectral contents of local field potentials in cortico-basal ganglia-thalamic circuits following treatment with this novel group of 5-HT1A agonists or the prototypical agonist, 8-OH-DPAT. Dyskinetic symptoms were consistently associated with 80 Hz oscillations, which were efficaciously suppressed by all 5-HT1A agonists and reappeared upon co-administration of the antagonist, WAY100635. At the same time, the peak-frequency of fast 130 Hz gamma oscillations and their cross-frequency coupling to low-frequency delta oscillations were modified to a different extent by each of the 5-HT1A agonists. These findings suggest that the common antidyskinetic effects of these drugs may be chiefly attributable to a reversal of the brain state characterized by 80 Hz gamma oscillations, whereas the differential effects on fast gamma oscillations may reflect differences in pharmacological properties that might be of potential relevance for non-motor symptoms.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
6-OHDA rat, Dyskinesia, Local field potential, Oscillations, Parkinson's disease, Systems neurophysiology
in
Experimental Neurology
volume
302
pages
14 pages
publisher
Academic Press
external identifiers
  • scopus:85041468451
ISSN
0014-4886
DOI
10.1016/j.expneurol.2018.01.010
language
English
LU publication?
yes
id
53731d37-cf3b-41f5-bb53-8e7d70f787d9
date added to LUP
2018-02-20 11:08:36
date last changed
2018-05-29 12:08:55
@article{53731d37-cf3b-41f5-bb53-8e7d70f787d9,
  abstract     = {<p>Recently, the biased and highly selective 5-HT<sub>1A</sub> agonists, NLX-112, F13714 and F15599, have been shown to alleviate dyskinesia in rodent and primate models of Parkinson's disease, while marginally interfering with antiparkinsonian effects of levodopa. To provide more detailed information on the processes underlying the alleviation of dyskinesia, we have here investigated changes in the spectral contents of local field potentials in cortico-basal ganglia-thalamic circuits following treatment with this novel group of 5-HT<sub>1A</sub> agonists or the prototypical agonist, 8-OH-DPAT. Dyskinetic symptoms were consistently associated with 80 Hz oscillations, which were efficaciously suppressed by all 5-HT<sub>1A</sub> agonists and reappeared upon co-administration of the antagonist, WAY100635. At the same time, the peak-frequency of fast 130 Hz gamma oscillations and their cross-frequency coupling to low-frequency delta oscillations were modified to a different extent by each of the 5-HT<sub>1A</sub> agonists. These findings suggest that the common antidyskinetic effects of these drugs may be chiefly attributable to a reversal of the brain state characterized by 80 Hz gamma oscillations, whereas the differential effects on fast gamma oscillations may reflect differences in pharmacological properties that might be of potential relevance for non-motor symptoms.</p>},
  author       = {Brys, Ivani and Halje, Pär and Scheffer-Teixeira, Robson and Varney, Mark and Newman-Tancredi, Adrian and Petersson, Per},
  issn         = {0014-4886},
  keyword      = {6-OHDA rat,Dyskinesia,Local field potential,Oscillations,Parkinson's disease,Systems neurophysiology},
  language     = {eng},
  month        = {04},
  pages        = {155--168},
  publisher    = {Academic Press},
  series       = {Experimental Neurology},
  title        = {Neurophysiological effects in cortico-basal ganglia-thalamic circuits of antidyskinetic treatment with 5-HT<sub>1A</sub> receptor biased agonists},
  url          = {http://dx.doi.org/10.1016/j.expneurol.2018.01.010},
  volume       = {302},
  year         = {2018},
}