Exogenous corticosterone reduces L-DOPA-induced dyskinesia in the hemi-parkinsonian rat:: Role for interleukin-1β

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 naive 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-1 ra) was microinjected into the striatum Of L-DOPA-primed rats to assess the impact of IL-1 signaling on LID. Intrastriatal IL-1 ra 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) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.