Subthalamic 6-OHDA-induced lesion attenuates levodopa-induced dyskinesias in the rat model of Parkinson's disease

The subthalamic nucleus (STN) receives direct dopaminergic innervation from the substantia nigra pars compacta that degenerates in Parkinson's disease. The present study aimed to investigate the role of dopaminergic denervation of STN in the origin of levodopa-induced dyskinesias. Rats were dis...

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Bibliographic Details
Published in:Experimental neurology 2013-12, Vol.250, p.304-312
Main Authors: Marin, C., Bonastre, M., Mengod, G., Cortés, R., Rodríguez-Oroz, M.C., Obeso, J.A.
Format: Article
Language:English
Subjects:
6-Hydroxydopamine
Animals
Antiparkinson Agents - adverse effects
Basal ganglia
Biological and medical sciences
Cytochrome oxidase
Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases
Drug toxicity and drugs side effects treatment
Dyskinesia
Dyskinesia, Drug-Induced - physiopathology
In Situ Hybridization
Levodopa - adverse effects
Male
Medical sciences
Nervous system (semeiology, syndromes)
Nervous system as a whole
Neurology
Parkinson's disease
Parkinsonian Disorders - physiopathology
Pharmacology. Drug treatments
Preprodynorphin
Preproenkephalin
Rats
Rats, Sprague-Dawley
Subthalamic nucleus
Subthalamic Nucleus - physiopathology
Toxicity: nervous system and muscle
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Summary:The subthalamic nucleus (STN) receives direct dopaminergic innervation from the substantia nigra pars compacta that degenerates in Parkinson's disease. The present study aimed to investigate the role of dopaminergic denervation of STN in the origin of levodopa-induced dyskinesias. Rats were distributed in four groups which were concomitantly lesioned with 6-OHDA or vehicle (sham) in the STN and in the medial forebrain bundle (MFB) as follows: a) MFB-sham plus STN-sham, b) MFB-sham plus STN-lesion, c) MFB-lesion plus STN-sham, and d) MFB-lesion plus STN-lesion. Four weeks after lesions, animals were treated with levodopa (6mg/kg with 15mg/kg benserazide i.p.) twice daily for 22 consecutive days. Abnormal involuntary movements were measured. In situ hybridization was performed measuring the expression of striatal preproenkephalin, preprodynorphin, STN cytochrome oxidase (CO) and nigral GAD67 mRNAs. STN 6-OHDA denervation did not induce dyskinesias in levodopa-treated MFB-sham animals but attenuated axial (p
ISSN:0014-4886
1090-2430
DOI:10.1016/j.expneurol.2013.10.006