The effects of treadmill training in hemi-parkinsonian rats

Abstract

The purpose of this study was to investigate whether locomotor training, in the form of treadmill training, could ameliorate neurochemical changes and behavioural deficits in the 6-hydroxydopamine (6-OHDA) rat model of Parkinson’s disease. It has been recently demonstrated that rehabilitative forelimb motor training can attenuate dopamine loss and some deficits in forelimb movements in this animal model. In addition, brief locomotor treadmill training has been shown to attenuate forelimb deficits in 6-OHDA treated rats. However, it is not known whether locomotor training could result in an amelioration of locomotor deficits in these animals. Rats were lesioned with 6-OHDA injected intracerebrally. Lesioned rats were randomly assigned to one of 3 groups: early treadmill trained, late treadmill trained and untrained. Animals in the treadmill groups were trained to trot on a moving treadmill for 2 x 20 minute sessions daily for 30 days, beginning either 24 hours or 7 days after 6-OHDA injection. Untrained animals were exposed to a stationary treadmill for the same time periods. All animals were assessed on their abilities to perform several behavioural tasks designed to test locomotor and forelimb movement abilities prior to 6-OHDA injection and again at 3 and 6 weeks post-injection. These tests included measurement of ground reaction forces during overground locomotion, paw placements during a ladder crossing task, forelimb useage during exploratory behaviour and ability to initiate forelimb stepping movements. In addition, assessments of dopamine depletion in the striatum were carried out first in vivo, by measuring apomorphine-induced rotations at 2 weeks post 6-OHDA injection, and subsequently by post-mortem analysis of dopamine levels in the striatum using HPLC at the conclusion of the study. Treadmill training resulted in attenuation of dopamine depletion compared to non-treadmill trained animals, as measured by both apomorphine injection and HPLC. However, treadmill training produced no difference in behavioural deficits on a variety of tests compared to untrained animals. In some cases, early treadmill trained animals tended to display more severe behavioural deficits compared to untrained animals. Late treadmill training had a similar but smaller effect compared to early treadmill training. We conclude that treadmill training does not ameliorate locomotor deficits, in the 6-OHDA model of Parkinson’s disease, even though this same training results in attenuation of dopamine loss in the striatum

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