Treadmill training ameliorates dopamine loss but not behavioral deficits in hemi-Parkinsonian rats

The purpose of this study was to investigate whether locomotor training could ameliorate neurochemical changes and behavioral deficits in the 6-hydroxydopamine (6-OHDA) rat model of Parkinson's disease. It has been recently demonstrated that forelimb motor training, or brief treadmill training, can attenuate dopamine loss and some deficits in forelimb usage in this animal model. Nevertheless, it is not known whether locomotor training could result in an amelioration of locomotor deficits. Rats were lesioned with 6-OHDA injected intracerebrally and randomly assigned to one of 3 groups: early treadmill trained, late treadmill trained and untrained. Animals in the early trained group underwent 2 × 20 min treadmill sessions daily for 30 days, beginning 24 h after 6-OHDA injection. Late trained animals underwent the same training regime beginning 7 days post-injection. All animals were assessed on their abilities to perform several behavioral tasks designed to test locomotor and forelimb movement abilities prior to 6-OHDA injection and at 3 and 6 weeks post-injection. Treadmill training resulted in the attenuation of dopamine depletion in the striatum compared to non-treadmill trained animals, as measured by in vivo apomorphine-induced rotations and post-mortem dopamine analysis. Nevertheless, treadmill training produced essentially no difference in behavioral deficits on most tests compared to untrained animals. We discuss the possible reasons for the discrepancies with previous studies, including differences in lesioning, training regimes and methods of behavioral assessment. 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.