Tio2-dopamine complex implanted unilaterally in the caudate nucleus improves motor activity and behavior function of rats with induced hemiparkinsonism.

Parkinson's disease (PD) is characterized by malfunction of dopaminergic systems, and the current symptomatic treatment is to replace lost dopamine. For investigating mechanisms of pathogenesis and alternative treatments to compensate lack of dopamine (DA) activity in PD, the 6-hydroxydopamine (6-OHDA)-lesioned rat model of PD has been useful, these animals display apomorphine-induced contralateral rotational behavior, when they are examined after lesion. The purpose of this study was to assess Titania-dopamine (TiO2-DA) complexes implanted on the caudate nucleus for diminishing motor behavior alterations of the 6-OHDA rat model. Rats with 6-OHDA unilateral lesions received TiO2 alone or TiO2-DA implants, and were tested for open field (OF) gross motor crossing and rearing behaviors, and apomorphine-induced rotation (G) behavior. TiO2 complex have no effects on rearing OF and G behaviors, and a significant reducing effect on crossing motor behavior of normal rats compared to control non-treated rats throughout 56 days of observation. Interestingly, TiO2-DA treatment significant recovered motor crossing and rearing behaviors in 6-OHDA-lesioned rats, and diminished the G behaviors during 56 days of examination. Additionally, in the 6-OHDA-lesioned rats TiO2 treatment had a moderate recovering effect only on crossing behavior compared to lesioned non treated rats. Our results suggest that continuous release of dopamine in the caudate nucleus from TiO2-DA complex is capable of reversing gross motor deficits observed in the 6-OHDA-lesioned rat model of PD. Thistype of delivery system of DA represents a promising therapy for PD in humans.

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

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 unilateral lesion, 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.