Role of striatal l-DOPA in the production of dyskinesia in 6-hydroxydopamine lesioned rats.
Carta, Manolo LU ; Lindgren, Hanna LU ; Lundblad, Martin LU ; Stancampiano, Roberto ; Fadda, Fabio and Cenci Nilsson, Angela LU
(2006)
In Journal of Neurochemistry
96(6).
p.1718-1727
- Abstract
- We explored possible differences in the peripheral and central pharmacokinetics of L-DOPA as a basis for individual variation in the liability to dyskinesia. Unilaterally, 6-hydroxydopamine (6-OHDA) lesioned rats were treated chronically with L-DOPA for an induction and monitoring of abnormal involuntary movements (AIMs). Comparisons between dyskinetic and non-dyskinetic cases were then carried out with regard to plasma and striatal L-DOPA concentrations, tissue levels of dopamine (DA), DA metabolites, and serotonin. After a single intraperitoneal injection of L-DOPA, plasma L-DOPA concentrations did not differ between dyskinetic and non-dyskinetic animals, whereas peak levels of L-DOPA in the striatal extracellular fluid were about... (More)
- We explored possible differences in the peripheral and central pharmacokinetics of L-DOPA as a basis for individual variation in the liability to dyskinesia. Unilaterally, 6-hydroxydopamine (6-OHDA) lesioned rats were treated chronically with L-DOPA for an induction and monitoring of abnormal involuntary movements (AIMs). Comparisons between dyskinetic and non-dyskinetic cases were then carried out with regard to plasma and striatal L-DOPA concentrations, tissue levels of dopamine (DA), DA metabolites, and serotonin. After a single intraperitoneal injection of L-DOPA, plasma L-DOPA concentrations did not differ between dyskinetic and non-dyskinetic animals, whereas peak levels of L-DOPA in the striatal extracellular fluid were about fivefold larger in the former compared with the latter group. Interestingly, the time course of the AIMs paralleled the surge in striatal L-DOPA levels. Intrastriatal infusion of L-DOPA by reverse dialysis concentration dependently induced AIMs in all 6-OHDA lesioned rats, regardless of a previous priming for dyskinesia. Steady-state levels of DA and its metabolites in striatal and cortical tissue did not differ between dyskinetic and non-dyskinetic animals, indicating that the observed difference in motor response to L-DOPA did not depend on the extent of lesion-induced DA depletion. These results show that an elevation of L-DOPA levels in the striatal extracellular fluid is necessary and sufficient for the occurrence of dyskinesia. Individual differences in the central bioavailability of L-DOPA may provide a clue to the varying susceptibility to dyskinesia in Parkinson's disease. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/154583
- author
- Carta, Manolo
LU
; Lindgren, Hanna
LU
; Lundblad, Martin
LU
; Stancampiano, Roberto
; Fadda, Fabio
and Cenci Nilsson, Angela
LU
- organization
- publishing date
- 2006
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Neurochemistry
- volume
- 96
- issue
- 6
- pages
- 1718 - 1727
- publisher
- Wiley-Blackwell
- external identifiers
-
- pmid:16539687
- wos:000235842100021
- scopus:33644813224
- pmid:16539687
- ISSN
- 1471-4159
- DOI
- 10.1111/j.1471-4159.2006.03696.x
- language
- English
- LU publication?
- yes
- id
- 042bbe20-4aad-487c-ad35-0bd2bcab5304 (old id 154583)
- alternative location
- http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16539687&dopt=Abstract
- date added to LUP
- 2016-04-01 16:48:37
- date last changed
- 2022-04-23 00:38:57
@article{042bbe20-4aad-487c-ad35-0bd2bcab5304,
abstract = {{We explored possible differences in the peripheral and central pharmacokinetics of L-DOPA as a basis for individual variation in the liability to dyskinesia. Unilaterally, 6-hydroxydopamine (6-OHDA) lesioned rats were treated chronically with L-DOPA for an induction and monitoring of abnormal involuntary movements (AIMs). Comparisons between dyskinetic and non-dyskinetic cases were then carried out with regard to plasma and striatal L-DOPA concentrations, tissue levels of dopamine (DA), DA metabolites, and serotonin. After a single intraperitoneal injection of L-DOPA, plasma L-DOPA concentrations did not differ between dyskinetic and non-dyskinetic animals, whereas peak levels of L-DOPA in the striatal extracellular fluid were about fivefold larger in the former compared with the latter group. Interestingly, the time course of the AIMs paralleled the surge in striatal L-DOPA levels. Intrastriatal infusion of L-DOPA by reverse dialysis concentration dependently induced AIMs in all 6-OHDA lesioned rats, regardless of a previous priming for dyskinesia. Steady-state levels of DA and its metabolites in striatal and cortical tissue did not differ between dyskinetic and non-dyskinetic animals, indicating that the observed difference in motor response to L-DOPA did not depend on the extent of lesion-induced DA depletion. These results show that an elevation of L-DOPA levels in the striatal extracellular fluid is necessary and sufficient for the occurrence of dyskinesia. Individual differences in the central bioavailability of L-DOPA may provide a clue to the varying susceptibility to dyskinesia in Parkinson's disease.}},
author = {{Carta, Manolo and Lindgren, Hanna and Lundblad, Martin and Stancampiano, Roberto and Fadda, Fabio and Cenci Nilsson, Angela}},
issn = {{1471-4159}},
language = {{eng}},
number = {{6}},
pages = {{1718--1727}},
publisher = {{Wiley-Blackwell}},
series = {{Journal of Neurochemistry}},
title = {{Role of striatal l-DOPA in the production of dyskinesia in 6-hydroxydopamine lesioned rats.}},
url = {{http://dx.doi.org/10.1111/j.1471-4159.2006.03696.x}},
doi = {{10.1111/j.1471-4159.2006.03696.x}},
volume = {{96}},
year = {{2006}},
}