Experimental Design
After surgery, all rats were allowed to recover for two weeks. L-DOPA or vehicle treatment started two days after the apomorphine rotational test. Animals were assigned randomly to experimental groups that were well-matched regarding the rotational rate (results not shown). Each experimental group was daily treated with L-DOPA (20 mg kg-1) plus benserazide–HCl (5 mg kg-1) or saline by gavage once a day for 15 days. The study consisted of four different main experiments.
Experiment 1- Impact of acute administration of doxycycline on LID expression once dyskinesia was present
In this experiment, group 6-OHDA+vehicle+L-DOPA (n=11) treated animals received L-DOPA for 14 days. On day 15, 50% of the animals received acute doxycycline (40 mg kg-1, i.p., once), 30 min before L-DOPA (6-OHDA+doxycycline+L-DOPA, n=6). The other parkinsonian animals received vehicle before L-DOPA (6-OHDA+vehicle+L-DOPA, n=5). After 3 days of drug washout, the allocation of the animals to “drug” versus “vehicle” treatment was switched. Therefore, each animal was submitted to both treatments. A comparison between the AIMs scores among the 6-OHDA+doxycycline+L-DOPA and 6-OHDA+vehicle+LDOPA groups was performed using a one-way repeated measures analysis of variance (ANOVA-RM).
An additional group of parkinsonian animals received similar treatment to those described above underwent the motor activity tests, the forepaw adjusting step, and the open field test. Experimental groups were composed of animals with already established LID: 6-OHDA+vehicle+L-DOPA (n=11) and 6-OHDA+doxycycline+L-DOPA (n=11). Comparisons of the AIMs scores between the experimental groups were performed by one-way ANOVA, followed by Bonferroni’s multiple comparisons test. The control groups were no-lesion+vehicle+vehicle (n=6); 6-OHDA+vehicle+vehicle, (n=8); 6-OHDA+doxycycline+ vehicle (n=9).