title: Combined ipsilateral limb use score as an index of motor deficits and neurorestoration in parkinsonian rats.
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.
authors.affiliation: School of Pharmacy (Pharmacology), University of Eastern Finland, P.O. Box 1627, FI-70211, Kuopio, Finland.
authors.forename: Juuso V
authors.identifier: 0000-0001-7868-9766
authors.initials: JV
authors.lastname: Leikas
authors.affiliation: School of Pharmacy (Pharmacology), University of Eastern Finland, P.O. Box 1627, FI-70211, Kuopio, Finland.|Present address: Orion Corporation Orion Pharma, P.O. Box 425, FI-20101, Turku, Finland.
authors.forename: Tiina M
authors.initials: TM
authors.lastname: Kääriäinen
authors.affiliation: School of Pharmacy (Pharmacology), University of Eastern Finland, P.O. Box 1627, FI-70211, Kuopio, Finland.
authors.forename: Aaro J
authors.initials: AJ
authors.lastname: Jalkanen
authors.affiliation: School of Pharmacy (Pharmacology), University of Eastern Finland, P.O. Box 1627, FI-70211, Kuopio, Finland.
authors.forename: Marko
authors.initials: M
authors.lastname: Lehtonen
authors.affiliation: Neuroscience Center, University of Helsinki, P.O. Box 56, FI-00790, Helsinki, Finland.|Faculty of Biological and Environmental Sciences, Department of Biosciences, Division of Physiology and Neuroscience, University of Helsinki, P.O. Box 56, FI-00790, Helsinki, Finland.
authors.forename: Tomi
authors.initials: T
authors.lastname: Rantamäki
authors.affiliation: School of Pharmacy (Pharmacology), University of Eastern Finland, P.O. Box 1627, FI-70211, Kuopio, Finland.
authors.forename: Markus M
authors.initials: MM
authors.lastname: Forsberg
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects*; D018492:Dopamine Antagonists / Q000008:administration & dosage / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D000068079:Motor Disorders / Q000139:chemically induced* / Q000209:etiology*; D016627:Oxidopamine / Q000008:administration & dosage / Q000633:toxicity; D020734:Parkinsonian Disorders / Q000139:chemically induced* / Q000150:complications*; D051381:Rats
chemical_list: D018492:Dopamine Antagonists; D016627:Oxidopamine
keywords: Parkinson's disease; dopamine; exercise; motor deficit; partial 6-OHDA lesion; sensorimotor test