DISCUSSION (1595 words)
The acute administration of doxycycline or COL-3 demonstrated an anti-dyskinetic effect in rats with already established LID. Notably, we demonstrated that co-administration of doxycycline with L-DOPA since the first day of receiving L-DOPA suppressed the development of AIMs. Our results demonstrate that doxycycline or COL-3 are useful complements to L-DOPA, in that they block LID but maintain the improvements in motor function.
Doxycycline attenuated the increase in FosB, COX-2, GFAP, and OX42 expression in the lesioned striatum induced by L-DOPA treatment. The results demonstrated an increase in MMP-2/MMP-9 activity and ROS presence in the striatum of L-DOPA-dyskinetic parkinsonian rats. Treatment with doxycycline decreased MMP-2/MMP-9 activity and ROS induced by L-DOPA treatment. The increase of ROS and MMP-2/MMP-9 activity was positively correlated with the degree of dyskinesia. Acute doxycycline treatment decreased MMP-9 gel detection related to LID, while chronic treatment decreased MMP2 and MMP-9 detection.
In agreement with our hypothesis, the modulation of inflammatory processes aimed at preventing or interrupting the cycle between damaged dopamine neurons, L-DOPA-treatment and dysregulated inflammation has the potential to emerge as a novel therapeutic strategy.