Preparation and assessment of the behavior of the rat model of levodopa-induced dyskinesias / 中华物理医学与康复杂志

ABSTRACT

Objective To study the behavioral characteristics of a rat model of the levodopa-induced dyskinesia (LID) and the related factors, and to define clinically the relevant methods for assessing akinesia and dyskinesia in LID rats. Methods Unilaterally lesioned rat model of Parkinson′s disease using 6-hydroxydopamine were treated by levodopa and benserazide once daily for 3 weeks, on the 21st day the acute systemic administration of MK-801 was performed 15 min prior to levodopa treatment to observe the behavior (abnormal involuntary movement, rotation behavior and forelimb stepping) and to estimate the quality of AIM by using the rat AIM rating scale. Immunohistochemical technique was used to measure the number of TH-positive neurons in the substantia nigra (SN) and ventral tegmental area (VTA), which was then correlated to the AIM scores. Results Pulsatile treatment with a subthreshold dose of levodopa gradually induced abnormal involuntary movement (AIM), including stereotypy (limb dyskinesia, axial dystonia and masticatory dyskinesia) towards the side contralateral to the dopamine-denervated striatum and increased rotational behavior. The onset of AIM and motor pattern of each subtype was highly stereotypic across individual rats, and the proportion of each subtype was not consistent among individual rats. The number of TH-positive neurons in the VTA, but not in the SN, was significantly decreased in the LID rats compared with the non-LID rats. MK-801 prevented stereotypy but not rotational behavior. Contralateral forepaw performance was signi-ficantly improved after levodopa treatment, but gradually reduced with more and more severe AIM following repeated levodopa therapy. Conclusion Levodopa-induced rat AIM model of PD demonstrated similar properties with the levodopa-induced dyskinesia (LID) in PD patients, and provided an effective tool for LID study. AIM rating and forelimb stepping test are useful for evaluating the dyskinesia and akinesia of PD rats.