Late aging-associated increases in L-DOPA-induced dyskinesia are accompanied by heightened neuroinflammation in the hemi-parkinsonian rat.

Aging is a primary risk factor for the development of Parkinson's disease (PD), and aging differentially predicts the incidence of L-DOPA-induced dyskinesia (LID). The goal of this work was to establish whether late aging-associated exacerbation of LID would be related to neuroinflammation in the hemi-parkinsonian rat. Two studies were conducted in which adult (3 months) and aged (18 months) male Fischer 344 rats bearing unilateral 6-hydroxydopamine lesions of the medial forebrain bundle were injected acutely with vehicle or L-DOPA (6 mg/kg). LID was quantified, and neuroinflammation was assessed postmortem via gene expression markers in the striatum (experiment 1) or through concurrent large-molecule microdialysis (experiment 2). In addition to exacerbating LID despite similar levels of striatal dopamine loss, late aging was associated with persistently elevated IL-1β gene expression ipsilateral to lesion, as well as a trend toward greater extracellular concentrations of IL-1β in response to acute L-DOPA treatment. In contrast, aged sham-operated rats displayed greater extracellular IL-6. Taken together, these data demonstrate an age-related vulnerability to LID and highlight potential neuroinflammatory mediators associated with these effects.