title: Exogenous corticosterone reduces L-DOPA-induced dyskinesia in the hemi-parkinsonian rat: role for interleukin-1beta.
abstract: 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.
authors.affiliation: Behavioral Neuroscience Program, Department of Psychology, State University of New York at Binghamton, 4400 Vestal Parkway East, Binghamton, NY 13902, USA.
authors.forename: C J
authors.initials: CJ
authors.lastname: Barnum
authors.forename: K L
authors.initials: KL
authors.lastname: Eskow
authors.forename: K
authors.initials: K
authors.lastname: Dupre
authors.forename: P
authors.initials: P
authors.lastname: Blandino
authors.forename: T
authors.initials: T
authors.lastname: Deak
authors.forename: C
authors.initials: C
authors.lastname: Bishop
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D003342:Corpus Striatum / Q000187:drug effects / Q000276:immunology / Q000503:physiopathology; D003345:Corticosterone / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D004660:Encephalitis / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D053590:Interleukin 1 Receptor Antagonist Protein / Q000494:pharmacology; D053583:Interleukin-1beta / Q000276:immunology*; D007980:Levodopa / Q000009:adverse effects*; D008297:Male; D008474:Medial Forebrain Bundle / Q000187:drug effects / Q000503:physiopathology; D009434:Neural Pathways / Q000187:drug effects / Q000276:immunology / Q000503:physiopathology; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000187:drug effects / Q000276:immunology / Q000503:physiopathology; D013565:Sympatholytics; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta; D012333:RNA, Messenger; D013565:Sympatholytics; D007980:Levodopa; D016627:Oxidopamine; D003345:Corticosterone