| Abstract: | Our aim was to apply a robust non‐drug induced sensorimotor test battery to assess the efficacy of neurorestorative therapies on the motor deficits caused by partial unilateral 6‐OHDA lesion mimicking early stage PD. Since the 6‐OHDA lesion protocols to induce partial DA depletion in striatum vary extensively between laboratories, we evaluated the associations between different intrastriatal 6‐OHDA doses (1 X 0‐20 and 2 X 0‐30 µg), striatal DA depletion (HPLC‐ECD) and D‐amphetamine induced rotation to identify a lesion protocol that would produce 40‐60% striatal DA depletion. Doses ≥ 6 µg produced a significant DA depletion (ANOVA, P < 0.0001). 6‐OHDA dose range (6‐14 µg) causing 40‐60% DA depletion induced very variable rotational responses. Next, intrastriatal 1 × 10 and 1 × 14 µg doses were compared with a full lesion (10 µg into the medial forebrain bundle) with regard to their effects on adjusting step, cylinder, and vibrissae test performance. A combined ipsilateral score (average of each test) was found more sensitive in distinguishing between different lesions than any test alone. Finally, five‐week treadmill exercise starting two weeks post‐lesion was able to restore impaired limb use (combined score; mixed model, P < 0.05) and striatal DA depletion (ANOVA, P < 0.05) in rats with partial lesion (1 × 10 µg). Notably, D‐amphetamine induced rotation significantly decreased between weeks one to seven post‐lesion (t‐test, P < 0.01). In conclusion, intrastriatal 1 × 10 µg of 6‐OHDA produces 40‐60% striatal DA depletion robustly, and the combined ipsilateral score provides an efficient means for testing of the efficacy of neurorestorative or neuroprotective treatments for PD. © 2017 Wiley Periodicals, Inc. |
