metastat and Dyskinesia--Drug-Induced

l-DOPA-induced dyskinesia is a debilitating effect of treating Parkinson's disease with this drug. New therapeutic approaches that prevent or attenuate this side effect are needed.. Wistar adult male rats submitted to 6-hydroxydopamine-induced unilateral medial forebrain bundle lesion were treated with l-DOPA (p.o. 20 mg·kg. A single injection of doxycycline or COL-3 attenuated l-DOPA-induced dyskinesia. Co-treatment with doxycycline from the first day of l-DOPA suppressed the onset of dyskinesia. The improved motor response after l-DOPA was not affected by doxycycline or COL-3. Doxycycline treatment was associated with decreased immunoreactivity of FosB, COX-2, the astroglial protein GFAP and the microglial protein OX-42, which were elevated in the basal ganglia of rats exhibiting dyskinesia. Doxycycline decreased metalloproteinase-2/-9 activity, metalloproteinase-3 expression and ROS production. Metalloproteinase-2/-9 activity and production of ROS in the basal ganglia of dyskinetic rats showed a significant correlation with the intensity of dyskinesia.. The present study demonstrates the anti-dyskinetic potential of doxycycline and its analogue compound COL-3 in hemiparkinsonian rats. Given the long-established and safe clinical use of doxycycline, this study suggests that these drugs might be tested to reduce or prevent l-DOPA-induced dyskinesia in Parkinson's patients.

Topics: Animals; Antiparkinson Agents; Corpus Striatum; Disease Models, Animal; Doxycycline; Dyskinesia, Drug-Induced; Levodopa; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 3; Matrix Metalloproteinase 9; Oxidopamine; Rats; Rats, Sprague-Dawley; Rats, Wistar; Reactive Oxygen Species; Tetracyclines