Dopamine release from serotonergic nerve fibers is reduced in L-DOPA-induced dyskinesia.
(2011) In Journal of Neurochemistry 118. p.12-23- Abstract
- l-DOPA is the most commonly used treatment for symptomatic control in patients with Parkinson's disease. Unfortunately, most patients develop severe side-effects, such as dyskinesia, upon chronic l-DOPA treatment. The patophysiology of dyskinesia is unclear; however, involvement of serotonergic nerve fibers in converting l-DOPA to dopamine has been suggested. Therefore, potassium-evoked dopamine release was studied after local application of l-DOPA in the striata of normal, dopamine- and dopamine/serotonin-lesioned l-DOPA naïve, and dopamine-denervated chronically l-DOPA-treated dyskinetic rats using in vivo chronoamperometry. The results revealed that local l-DOPA administration into normal and intact hemisphere of dopamine-lesioned... (More)
- l-DOPA is the most commonly used treatment for symptomatic control in patients with Parkinson's disease. Unfortunately, most patients develop severe side-effects, such as dyskinesia, upon chronic l-DOPA treatment. The patophysiology of dyskinesia is unclear; however, involvement of serotonergic nerve fibers in converting l-DOPA to dopamine has been suggested. Therefore, potassium-evoked dopamine release was studied after local application of l-DOPA in the striata of normal, dopamine- and dopamine/serotonin-lesioned l-DOPA naïve, and dopamine-denervated chronically l-DOPA-treated dyskinetic rats using in vivo chronoamperometry. The results revealed that local l-DOPA administration into normal and intact hemisphere of dopamine-lesioned l-DOPA naïve animals significantly increased the potassium-evoked dopamine release. l-DOPA application also increased the dopamine peak amplitude in the dopamine-depleted l-DOPA naïve striatum, although these dopamine levels were several-folds lower than in the normal striatum, whereas no increased dopamine release was found in the dopamine/serotonin-denervated striatum. In dyskinetic animals, local l-DOPA application did not affect the dopamine release, resulting in significantly attenuated dopamine levels compared with those measured in l-DOPA naïve dopamine-denervated striatum. To conclude, l-DOPA is most likely converted to dopamine in serotonergic nerve fibers in the dopamine-depleted striatum, but the dopamine release is several-fold lower than in normal striatum. Furthermore, l-DOPA loading does not increase the dopamine release in dyskinetic animals as found in l-DOPA naïve animals, despite similar density of serotonergic innervation. Thus, the dopamine overflow produced from the serotonergic nerve fibers appears not to be the major cause of dyskinetic behavior. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1973277
- author
- Nevalainen, Nina ; Af Bjerkén, Sara ; Lundblad, Martin LU ; Gerhardt, Greg A and Strömberg, Ingrid
- organization
- publishing date
- 2011
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Neurochemistry
- volume
- 118
- pages
- 12 - 23
- publisher
- Wiley-Blackwell
- external identifiers
-
- wos:000292656600003
- pmid:21534956
- scopus:80052541116
- ISSN
- 1471-4159
- DOI
- 10.1111/j.1471-4159.2011.07292.x
- language
- English
- LU publication?
- yes
- id
- 73f7b744-99b8-43f1-af57-94ac1ca84d82 (old id 1973277)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/21534956?dopt=Abstract
- date added to LUP
- 2016-04-04 09:19:25
- date last changed
- 2022-02-21 00:16:02
@article{73f7b744-99b8-43f1-af57-94ac1ca84d82,
abstract = {{l-DOPA is the most commonly used treatment for symptomatic control in patients with Parkinson's disease. Unfortunately, most patients develop severe side-effects, such as dyskinesia, upon chronic l-DOPA treatment. The patophysiology of dyskinesia is unclear; however, involvement of serotonergic nerve fibers in converting l-DOPA to dopamine has been suggested. Therefore, potassium-evoked dopamine release was studied after local application of l-DOPA in the striata of normal, dopamine- and dopamine/serotonin-lesioned l-DOPA naïve, and dopamine-denervated chronically l-DOPA-treated dyskinetic rats using in vivo chronoamperometry. The results revealed that local l-DOPA administration into normal and intact hemisphere of dopamine-lesioned l-DOPA naïve animals significantly increased the potassium-evoked dopamine release. l-DOPA application also increased the dopamine peak amplitude in the dopamine-depleted l-DOPA naïve striatum, although these dopamine levels were several-folds lower than in the normal striatum, whereas no increased dopamine release was found in the dopamine/serotonin-denervated striatum. In dyskinetic animals, local l-DOPA application did not affect the dopamine release, resulting in significantly attenuated dopamine levels compared with those measured in l-DOPA naïve dopamine-denervated striatum. To conclude, l-DOPA is most likely converted to dopamine in serotonergic nerve fibers in the dopamine-depleted striatum, but the dopamine release is several-fold lower than in normal striatum. Furthermore, l-DOPA loading does not increase the dopamine release in dyskinetic animals as found in l-DOPA naïve animals, despite similar density of serotonergic innervation. Thus, the dopamine overflow produced from the serotonergic nerve fibers appears not to be the major cause of dyskinetic behavior.}},
author = {{Nevalainen, Nina and Af Bjerkén, Sara and Lundblad, Martin and Gerhardt, Greg A and Strömberg, Ingrid}},
issn = {{1471-4159}},
language = {{eng}},
pages = {{12--23}},
publisher = {{Wiley-Blackwell}},
series = {{Journal of Neurochemistry}},
title = {{Dopamine release from serotonergic nerve fibers is reduced in L-DOPA-induced dyskinesia.}},
url = {{http://dx.doi.org/10.1111/j.1471-4159.2011.07292.x}},
doi = {{10.1111/j.1471-4159.2011.07292.x}},
volume = {{118}},
year = {{2011}},
}