Objective: To optimize a simple unilateral partial 6-hydroxydopamine (6-OHDA) lesion protocol that would produce 40-60% striatal dopamine (DA) depletion with detectable motor deficits and to evaluate the performance of the model by a neurorestorative intervention.

Background: Unilateral 6-OHDA infusion into rat striatum induces partial degeneration of nigrostriatal dopaminergic neurons and sensorimotor deficits that resemble human parkinsonism. Despite the model has been used extensively, optimal lesion protocol producing 40-60% DA depletion for testing of neurorestorative therapies has not been established.

Methods: Various intrastriatal 6-OHDA doses (3-60 µg) were infused unilaterally. Two weeks later, striatal DA depletion was assessed by HPLC. 6-OHDA induced motor deficits were assessed by D-amphetamine (2.5 mg/kg i.p.) induced rotation test, and by a sensorimotor test battery consisting of cylinder, adjusting step and vibrissae tests. On the basis of these studies, an optimal 6-OHDA dose (10 µg) was selected and the neurorestorative effects of walking exercise (30 min x 5 times/week for five weeks) were assessed.

Results: A single 10 µg intrastriatal 6-OHDA infusion produced 40-60% DA depletion in striatum. 6-OHDA dose range (6-14 µg) causing 40-60 % striatal DA depletion induced variable (50-500 ipsilateral rounds) rotational responses in D-amphetamine test. Instead, the ipsilateral limb use score (i.e. the average of ipsilateral limb use preference in the vibrissae, adjusting step and cylinder tests) was sensitive in distinguishing between different degrees of 6-OHDA lesions. The score was also able to detect the progression of motor deficits in the long term walking exercise study, and walking exerted significant neurorestorative effects in the model.

Conclusions: A single 10 µg intrastriatal 6-OHDA infusion can be considered as an optimal dose to induce a consistent partial lesion and it represents an animal model of early PD suitable for testing neurorestorative therapies aimed to restoring the functionality of a damaged nigrostriatal dopaminergic system. The combination of simple sensorimotor tests and overall ipsilateral limb use score provide a powerful means to assess sensorimotor performance of rats with unilateral partial 6-OHDA lesion in testing of the efficacy of novel neurorestorative treatments such as walking exercise in this study.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/optimization-of-6-hydroxydopamine-animal-model-of-early-stage-parkinsons-disease-for-the-assessment-of-neurorestorative-therapies/