Three days after apomorphine screening (Figure 2A ), 45 successful hemiparkinsonian rats received intraperitoneal injections of L-DOPA plus benserazide (12/6 mg/kg) once daily. L-DOPA-induced AIMs were recorded every other day. Rats were observed for 1 min every 35 min intervals for a total of 140 min following L-DOPA treatment. AIMs were evaluated using the validated AIMs scale. Orofacial, limb, and axial dyskinesia were graded from score 0 to 4: 0 = absent; 1 = occasional, present during less than half min; 2 = frequent, present during more than half min; 3 = continuous but interrupted by strong sensory distraction; 4 = continuous, not interrupted by strong sensory distraction (Winkler et al., 2002 (link); Lundblad et al., 2004 (link)). The total of axial, limb and orofacial dyskinesia was also named ALO dyskinesia and the maximum ALO dyskinesia score in each session was 48. Rotation (contralateral turns) test was performed as before (Breger et al., 2013 (link)) at day 1, 4, 12, 16, and 20, and only turns of completed 360° were counted.
From day 10, 42 rats with complete dyskinesia (ALO AIMs score = 12 at 70 min after L-DOPA) were divided into 3 groups: LID group, LID + PD98059 group, and LID + vehicle group. There was cannula implantation for each rat in the latter two groups. A volume of 3 μl PD98059 solution (0.4 μg/μl) or vehicle was infused into the right lateral ventricle over 6 min through the cannula connected to the microinjection system half hour before L-DOPA administration from day 10 to 21 (Figure2A ). The infusion needle was left in place for 2 min at the end of infusion for drug diffusion. Normal rats with sham operation and hemiparkinsonian rats were chosen as normal group and PD group, respectively. There were 14 rats in each group.
The stepping test was carried out 15 min before (pre-) and after (post-) L-DOPA treatment as previously described (Pinna et al., 2007 (link), 2010 (link)) on days 2, 10, and 18. Rats were moved on the surface of the table for 0.7 m in 4 s by the experimenter. The number of adjusting steps of left and right forelimbs in the forward directions was counted.
All behavioral tests were performed by a blinded examiner.
From day 10, 42 rats with complete dyskinesia (ALO AIMs score = 12 at 70 min after L-DOPA) were divided into 3 groups: LID group, LID + PD98059 group, and LID + vehicle group. There was cannula implantation for each rat in the latter two groups. A volume of 3 μl PD98059 solution (0.4 μg/μl) or vehicle was infused into the right lateral ventricle over 6 min through the cannula connected to the microinjection system half hour before L-DOPA administration from day 10 to 21 (Figure
The stepping test was carried out 15 min before (pre-) and after (post-) L-DOPA treatment as previously described (Pinna et al., 2007 (link), 2010 (link)) on days 2, 10, and 18. Rats were moved on the surface of the table for 0.7 m in 4 s by the experimenter. The number of adjusting steps of left and right forelimbs in the forward directions was counted.
All behavioral tests were performed by a blinded examiner.
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