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Open AccessArticle

Propranolol Relieves L-Dopa-Induced Dyskinesia in Parkinsonian Mice

1
Department of Pediatrics, Yale University, New Haven, CT 06510, USA
2
Departments of Neurology and Cellular and Molecular Physiology, Yale University, New Haven, CT 06510, USA
3
Department of Neurology, University of Washington, Seattle, WA 98105, USA
*
Author to whom correspondence should be addressed.
Brain Sci. 2020, 10(12), 903; https://doi.org/10.3390/brainsci10120903
Received: 26 October 2020 / Revised: 16 November 2020 / Accepted: 19 November 2020 / Published: 24 November 2020
(This article belongs to the Special Issue Novel Therapy for Movement Disorders)
Background: Parkinsonism is caused by dopamine (DA) insufficiency and results in a hypokinetic movement disorder. Treatment with L-Dopa can restore DA availability and improve motor function, but patients can develop L-Dopa-induced dyskinesia (LID), a secondary hyperkinetic movement disorder. The mechanism underlying LID remains unknown, and new treatments are needed. Experiments in mice have shown that DA deficiency promotes an imbalance between striatal acetylcholine (ACh) and DA that contributes to motor dysfunction. While treatment with L-Dopa improves DA availability, it promotes a paradoxical rise in striatal ACh and a further increase in the ACh to DA ratio may promote LID. Methods: We used conditional Slc6a3DTR/+ mice to model progressive DA deficiency and the β-adrenergic receptor (β-AR) antagonist propranolol to limit the activity of striatal cholinergic interneurons (ChIs). DA-deficient mice were treated with L-Dopa and the dopa decarboxylase inhibitor benserazide. LID and motor performance were assessed by rotarod, balance beam, and open field testing. Electrophysiological experiments characterized the effects of β-AR ligands on striatal ChIs. Results: LID was observed in a subset of DA-deficient mice. Treatment with propranolol relieved LID and motor hyperactivity. Electrophysiological experiments showed that β-ARs can effectively modulate ChI firing. Conclusions: The work suggests that pharmacological modulation of ChIs by β-ARs might provide a therapeutic option for managing LID. View Full-Text
Keywords: Parkinson’s disease; striatum; acetylcholine; cholinergic; interneuron; β-adrenergic; receptor; levodopa; dopa-responsive; dystonia Parkinson’s disease; striatum; acetylcholine; cholinergic; interneuron; β-adrenergic; receptor; levodopa; dopa-responsive; dystonia
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MDPI and ACS Style

Shi, Z.; Bamford, I.J.; McKinley, J.W.; Devi, S.P.S.; Vahedipour, A.; Bamford, N.S. Propranolol Relieves L-Dopa-Induced Dyskinesia in Parkinsonian Mice. Brain Sci. 2020, 10, 903. https://doi.org/10.3390/brainsci10120903

AMA Style

Shi Z, Bamford IJ, McKinley JW, Devi SPS, Vahedipour A, Bamford NS. Propranolol Relieves L-Dopa-Induced Dyskinesia in Parkinsonian Mice. Brain Sciences. 2020; 10(12):903. https://doi.org/10.3390/brainsci10120903

Chicago/Turabian Style

Shi, Ziqing; Bamford, Ian J.; McKinley, Jonathan W.; Devi, Suma P.S.; Vahedipour, Annie; Bamford, Nigel S. 2020. "Propranolol Relieves L-Dopa-Induced Dyskinesia in Parkinsonian Mice" Brain Sci. 10, no. 12: 903. https://doi.org/10.3390/brainsci10120903

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