Document Detail

Exogenous corticosterone reduces L-DOPA-induced dyskinesia in the hemi-parkinsonian rat: role for interleukin-1beta.
MedLine Citation:
PMID:  18687386     Owner:  NLM     Status:  MEDLINE    
While the etiology of Parkinson's disease (PD) remains unknown, there is overwhelming evidence that neuroinflammation plays a critical role in the progressive loss of dopamine (DA) neurons. Because nearly all persons suffering from PD receive l-DOPA, it is surprising that inflammation has not been examined as a potential contributor to the abnormal involuntary movements (AIMs) that occur as a consequence of chronic l-DOPA treatment. As an initial test of this hypothesis, we examined the effects of exogenously administered corticosterone (CORT), an endogenous anti-inflammatory agent, on the expression and development of l-DOPA-induced dyskinesia (LID) in unilateral DA-depleted rats. To do this, male Sprague-Dawley rats received unilateral medial forebrain bundle 6-hydroxydopamine lesions. Three weeks later, l-DOPA primed rats received acute injections of CORT (0-3.75 mg/kg) prior to l-DOPA to assess the expression of LID. A second group of rats was used to examine the development of LID in l-DOPA naïve rats co-treated with CORT and l-DOPA for 2 weeks. AIMs and rotations were recorded. Exogenous CORT dose-dependently attenuated both the expression and development of AIMs without affecting rotations. Real-time reverse-transcription polymerase chain reaction of striatal tissue implicated a role for interleukin-1 (IL-1) beta in these effects as its expression was increased on the lesioned side in rats treated with l-DOPA (within the DA-depleted striatum) and attenuated with CORT. In the final experiment, interleukin-1 receptor antagonist (IL-1ra) was microinjected into the striatum of l-DOPA-primed rats to assess the impact of IL-1 signaling on LID. Intrastriatal IL-1ra reduced the expression of LID without affecting rotations. These findings indicate a novel role for neuroinflammation in the expression of LID, and may implicate the use of anti-inflammatory agents as a potential adjunctive therapy for the treatment of LID.
C J Barnum; K L Eskow; K Dupre; P Blandino; T Deak; C Bishop
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2008-07-12
Journal Detail:
Title:  Neuroscience     Volume:  156     ISSN:  0306-4522     ISO Abbreviation:  Neuroscience     Publication Date:  2008 Sep 
Date Detail:
Created Date:  2008-09-15     Completed Date:  2009-01-05     Revised Date:  2014-09-21    
Medline Journal Info:
Nlm Unique ID:  7605074     Medline TA:  Neuroscience     Country:  United States    
Other Details:
Languages:  eng     Pagination:  30-41     Citation Subset:  IM    
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MeSH Terms
Anti-Inflammatory Agents / pharmacology,  therapeutic use
Corpus Striatum / drug effects,  immunology,  physiopathology
Corticosterone / pharmacology*,  therapeutic use
Disease Models, Animal
Dose-Response Relationship, Drug
Dyskinesia, Drug-Induced / drug therapy*,  immunology,  physiopathology
Encephalitis / complications,  drug therapy*,  immunology
Interleukin 1 Receptor Antagonist Protein / pharmacology
Interleukin-1beta / immunology*
Levodopa / adverse effects*
Medial Forebrain Bundle / drug effects,  physiopathology
Neural Pathways / drug effects,  immunology,  physiopathology
Parkinsonian Disorders / drug therapy*,  immunology,  physiopathology
RNA, Messenger / analysis,  metabolism
Rats, Sprague-Dawley
Substantia Nigra / drug effects,  immunology,  physiopathology
Up-Regulation / drug effects
Grant Support
Reg. No./Substance:
0/Anti-Inflammatory Agents; 0/Interleukin 1 Receptor Antagonist Protein; 0/Interleukin-1beta; 0/RNA, Messenger; 0/Sympatholytics; 46627O600J/Levodopa; 8HW4YBZ748/Oxidopamine; W980KJ009P/Corticosterone

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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