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Molecular Mechanisms of L-DOPA-Induced Dyskinesia

Cenci Nilsson, Angela LU (2017) In Handbook of Behavioral Neuroscience 24. p.857-871
Abstract

The dopamine (DA) precursor, 3,4-dihydroxyphenyl-L-alanine (L-DOPA), is the most effective treatment for Parkinson's disease (PD), but causes dyskinesias (abnormal involuntary movements) in the vast majority of patients. There is a wide consensus that L-DOPA-induced dyskinesia (LID) depends on both pre- and postsynaptic disturbances of the nigrostriatal DA transmission. Presynaptically, LID is associated with abnormal DA release and defective DA clearance, which converge to cause large swings in brain DA levels concomitant with the medication. Postsynaptically, LID is associated with a dysregulation of intracellular signaling and gene expression downstream of the D1 DA receptor. These phenomena are particularly well studied in the... (More)

The dopamine (DA) precursor, 3,4-dihydroxyphenyl-L-alanine (L-DOPA), is the most effective treatment for Parkinson's disease (PD), but causes dyskinesias (abnormal involuntary movements) in the vast majority of patients. There is a wide consensus that L-DOPA-induced dyskinesia (LID) depends on both pre- and postsynaptic disturbances of the nigrostriatal DA transmission. Presynaptically, LID is associated with abnormal DA release and defective DA clearance, which converge to cause large swings in brain DA levels concomitant with the medication. Postsynaptically, LID is associated with a dysregulation of intracellular signaling and gene expression downstream of the D1 DA receptor. These phenomena are particularly well studied in the striatum and are thus the main topic of this chapter. In addition, the chapter reviews studies that have revealed associations between LID and different types of abnormalities in glutamatergic and GABAergic transmission within cortico-basal ganglia circuits.

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author
organization
publishing date
type
Chapter in Book/Report/Conference proceeding
publication status
published
subject
keywords
animal models, dopamine, gene expression, glutamate, Neurodegenerative disease, neuroplasticity, Parkinson's disease, serotonin, striatum
in
Handbook of Behavioral Neuroscience
volume
24
pages
15 pages
publisher
The Association for the Study of Animal Behaviour / Elsevier B.V.
external identifiers
  • scopus:84998704789
ISSN
15697339
DOI
10.1016/B978-0-12-802206-1.00043-X
language
English
LU publication?
yes
id
12d805ec-c2a7-45b2-95ac-fe52dac9b4e0
date added to LUP
2017-03-17 09:52:42
date last changed
2017-03-17 09:52:42
@inbook{12d805ec-c2a7-45b2-95ac-fe52dac9b4e0,
  abstract     = {<p>The dopamine (DA) precursor, 3,4-dihydroxyphenyl-L-alanine (L-DOPA), is the most effective treatment for Parkinson's disease (PD), but causes dyskinesias (abnormal involuntary movements) in the vast majority of patients. There is a wide consensus that L-DOPA-induced dyskinesia (LID) depends on both pre- and postsynaptic disturbances of the nigrostriatal DA transmission. Presynaptically, LID is associated with abnormal DA release and defective DA clearance, which converge to cause large swings in brain DA levels concomitant with the medication. Postsynaptically, LID is associated with a dysregulation of intracellular signaling and gene expression downstream of the D1 DA receptor. These phenomena are particularly well studied in the striatum and are thus the main topic of this chapter. In addition, the chapter reviews studies that have revealed associations between LID and different types of abnormalities in glutamatergic and GABAergic transmission within cortico-basal ganglia circuits.</p>},
  author       = {Cenci Nilsson, Angela},
  issn         = {15697339},
  keyword      = {animal models,dopamine,gene expression,glutamate,Neurodegenerative disease,neuroplasticity,Parkinson's disease,serotonin,striatum},
  language     = {eng},
  pages        = {857--871},
  publisher    = {The Association for the Study of Animal Behaviour / Elsevier B.V.},
  series       = {Handbook of Behavioral Neuroscience},
  title        = {Molecular Mechanisms of L-DOPA-Induced Dyskinesia},
  url          = {http://dx.doi.org/10.1016/B978-0-12-802206-1.00043-X},
  volume       = {24},
  year         = {2017},
}