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  Differential effects of levodopa and apomorphine on neuronal population oscillations in the cortico-basal ganglia loop circuit in vivo in experimental parkinsonism

Kühn, J., Haumesser, J. K., Beck, M. H., Altschüler, J., Kühn, A. A., Nikulin, V. V., et al. (2017). Differential effects of levodopa and apomorphine on neuronal population oscillations in the cortico-basal ganglia loop circuit in vivo in experimental parkinsonism. Experimental Neurology, 298(Pt A), 122-133. doi:10.1016/j.expneurol.2017.09.005.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-002D-FD7E-0 Version Permalink: http://hdl.handle.net/21.11116/0000-0003-BD55-9
Genre: Journal Article

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 Creators:
Kühn, Johanna1, Author
Haumesser, Jens K.1, Author
Beck, Maximilian H.1, Author
Altschüler, Jennifer1, Author
Kühn, Andrea A.1, Author
Nikulin, Vadim V.1, 2, Author              
van Riesen, Christoph1, Author
Affiliations:
1Department of Neurology, Charité University Medicine Berlin, Germany, ou_persistent22              
2Department Neurology, MPI for Human Cognitive and Brain Sciences, Max Planck Society, ou_634549              

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Free keywords: Parkinson's disease; Beta oscillations; Gamma oscillations; Levodopa; Apomorphine; Cortico-basal ganglia loop
 Abstract: The current pharmacotherapy of Parkinson's disease (PD) is primarily based on two classes of drugs: dopamine precursors, namely levodopa, and dopamine receptor agonists, such as apomorphine. Although both types of agents exert their beneficial clinical effects on motor and non-motor symptoms in PD via dopamine receptors, clinical efficiency and side effects differ substantially between levodopa and apomorphine. Levodopa can provide a greater symptomatic relief than dopamine receptor agonists. However, because long-term levodopa use is associated with early debilitating motor fluctuations, dopamine receptor agonists are often recommended in younger patients. The pharmacodynamic basis of these profound differences is incompletely understood. It has been hypothesized that levodopa and dopamine receptor agonists may have diverging effects on beta and gamma oscillations that have been shown to be of importance for the pathophysiology of PD. Here, we used electrophysiological recordings in anesthetized dopamine-intact and dopamine-depleted rats to systemically compare the impact of levodopa or apomorphine on neuronal population oscillations in three nodes of the cortico-basal ganglia loop circuit. Our results showed that levodopa had a higher potency than apomorphine to suppress the abnormal beta oscillations often associated with bradykinesia while simultaneously enhancing the gamma oscillations often associated with increased movement. Our data suggests that the higher clinical efficacy of levodopa as well as some of its side effects, as e.g. dyskinesias may be based on its characteristic ability to modulate beta-/gamma-oscillation dynamics in the cortico-basal ganglia loop circuit.

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Language(s): eng - English
 Dates: 2017-09-032017-06-202017-09-072017-09-082017-12
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1016/j.expneurol.2017.09.005
PMID: 28893517
Other: Epub 2017
 Degree: -

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Project name : Tiefe Hirnstimulation: Wirkmechanismus, Kortex-Basalganglien - Physiologie und Therapieoptimierung / KFO 247
Grant ID : GE 2629/1-1
Funding program : -
Funding organization : Deutsche Forschungsgemeinschaft (DFG)

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Title: Experimental Neurology
  Other : Exp. Neurol.
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: San Diego, CA : Academic Press
Pages: - Volume / Issue: 298 (Pt A) Sequence Number: - Start / End Page: 122 - 133 Identifier: ISSN: 0014-4886
CoNE: /journals/resource/991042743109584