Neurophysiological effects in cortico-basal ganglia-thalamic circuits of antidyskinetic treatment with 5-HT1A receptor biased agonists
(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
- Brys, Ivani LU ; Halje, Pär LU ; Scheffer-Teixeira, Robson ; Varney, Mark ; Newman-Tancredi, Adrian and Petersson, Per LU
- organization
- publishing date
- 2018-04-01
- 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
- Elsevier
- external identifiers
-
- pmid:29339052
- 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
- 2024-04-01 01:15:30
@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}},
keywords = {{6-OHDA rat; Dyskinesia; Local field potential; Oscillations; Parkinson's disease; Systems neurophysiology}},
language = {{eng}},
month = {{04}},
pages = {{155--168}},
publisher = {{Elsevier}},
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}},
doi = {{10.1016/j.expneurol.2018.01.010}},
volume = {{302}},
year = {{2018}},
}