A novel skilled-reaching impairment in paw supination on the "good" side of the hemi-Parkinson rat improved with rehabilitation

Abstract

Parkinson's disease is characterized by tremor, rigidity, bradykinesia, and postural abnormalities ascribed to the loss of nigrostriatal dopamine (DA). Symptoms similar to the human condition can be produced in the rat by DA-depleting 6-hydroxydopamine injections made into the nigrostriatal system. After a unilaterallesion, the rat symptoms include sensory and motor impairments and turning biases reflecting motor abnormalities to the contralateral-to-depletion side of the body. In addition, a number of studies on skilled reaching report impairments in the use of the ipsilateral limb. It is suggested that the ipsilateral deficit is secondary to the contralateral motor impairments however. Here we re-examine how rats with unilateral DA depletion use their ipsilateral limb for skilled reaching for food. We provide the first description of an impairment on the ipsilateral-to-depletion side of the body of the rat and the first demonstration of amelioration of the defect using behavioral therapy. Video analysis of rats reaching for single pellets of food with the ipsilateral limb revealed that, although limb advancement and food grasping were normal, paw supination and food release to the mouth were impaired. Consequently, the animals were unable to transport a grasped food pellet to the mouth. Behavioral therapy, consisting of training in a simpler reaching task, strikingly lessened the impairment and improved reaching movements to the point that the rats could transport the food to the mouth. The results are discussed in relation to possible causes of the ipsilateral impairment, its treatment, and to relevant research on human Parkinson patients, indicating that they display bilateral improvements after unilateral treatments.