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Although extrastriatal dopaminergic (DAergic) systems are being recognized as contributors to Parkinson's disease (PD) pathophysiology, the role of extrastriatal DA depletion in L-Dopa-induced dyskinesia (LID) is still unknown. In view of the physiologic actions of DA on pallidal neuronal activity and the effects on motor behavior of local injection of DA drugs, the loss of the external (GPe, GP in rodents) and internal (GPi, entopeduncular nucleus (EP) in rodents) pallidal DAergic innervation might differentially contribute to LID. A role of pallidal serotonergic (SER) terminals in LID has been highlighted, however, the effect of DAergic innervation is unknown. We investigated the role of DAergic pallidal depletion on LID. Rats were distributed in groups which were concomitantly lesioned with 6-OHDA or vehicle (sham) in the GP, or EP, and in the medial forebrain bundle (MFB) as follows: a) MFB-sham+GP-sham, b) MFB-sham+GP-lesion, c) MFB-lesion+GP-sham, d) MFB-lesion+GP-lesion, e) MFB-sham+EP-sham, f) MFB-sham+EP-lesion, g) MFB-lesion+EP-sham, and h) MFB-lesion+EP-lesion. Four weeks later, animals were treated with L-Dopa (6 mg/kg) twice daily for 22 days.. Immunohistochemical studies were performed in order to investigate the changes in pallidal SER and serotonin transporter (SERT) levels. GP, but not EP, DAergic denervation attenuated LID in rats with a concomitant MFB lesion (p < 0.01). No differences were found in GP SERT expression between groups of animals developing or not LID. These results provide evidence of the relevance of GP DAergic innervation in LID. The conversion of levodopa to DA in GP serotonergic nerve fibers appears not to be the major mechanism underlying LID. Copyright © 2020 Elsevier Inc. All rights reserved.

Citation

Concepció Marin, Mercè Bonastre, Mireya Fuentes, Joaquim Mullol. Globus pallidus, but not entopeduncular nucleus, 6-OHDA-induced lesion attenuates L-Dopa-induced dyskinesia in the rat model of Parkinson's disease. Pharmacology, biochemistry, and behavior. 2020 Oct;197:173013

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PMID: 32758524

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