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).