Decreased forelimb ability in mice intracerebroventricularly injected with low dose 6-hydroxidopamine: A model on the dissociation of bradykinesia from hypokinesia.
Bradykinesia and hypokinesia represent well-known motor symptoms of Parkinson's disease (PD). While bradykinesia (slow execution of movements) is present in less affected PD patients and aggravates as the disease severity increases, hypokinesia (reduction of movement) seems to emerge prominently only in the more affected patients. Here we developed a model based on the central infusion of low dose (40μg) 6-hydroxydopamine (6-OHDA) in mice in an attempt to discriminate bradykinesia (accessed through forelimb inability) from hypokinesia (accessed through locomotor and exploratory activities). The potential beneficial effects of succinobucol against 6-OHDA-induced forelimb inability were also evaluated. One week after the beginning of treatment with succinobucol (i.p. injections, 10mg/kg/day), mice received a single i.c.v. infusion of 6-OHDA (40μg/site). One week after 6-OHDA infusion, general locomotor/exploratory activities (open field test), muscle strength (grid test), forelimb skill (single pellet task), as well as striatal biochemical parameters related to oxidative stress and cellular homeostasis (glutathione peroxidase, glutathione reductase and NADH dehydrogenases activities, lipid peroxidation and TH levels), were evaluated. 6-OHDA infusions did not change locomotor/exploratory activities and muscle strength, as well as the evaluated striatal biochemical parameters. However, 6-OHDA infusions caused significant reductions (50%) in the single pellet reaching task performance, which detects forelimb skill inability and can be used to experimentally identify bradykinesia. Succinobucol partially protected against 6-OHDA-induced forelimb inability. The decreased forelimb ability with no changes in locomotor/exploratory behavior indicates that our 6-OHDA-based protocol represents a useful tool to mechanistically study the dissociation of bradykinesia and hypokinesia in PD.
['Ribeiro|Renata Pietsch|RP|', 'Santos|Danúbia Bonfanti|DB|', 'Colle|Dirleise|D|', 'Naime|Aline Aita|AA|', 'Gonçalves|Cinara Ludvig|CL|', 'Ghizoni|Heloisa|H|', 'Hort|Mariana Appel|MA|', 'Godoi|Marcelo|M|', 'Dias|Paulo Fernando|PF|', 'Braga|Antonio Luiz|AL|', 'Farina|Marcelo|M|']
D018663:Adrenergic Agents D000818:Animals D004305:Dose-Response Relationship, Drug D005106:Exploratory Behavior D005247:Feeding Behavior D005552:Forelimb D005979:Glutathione Peroxidase D005980:Glutathione Reductase D015395:Histocompatibility Antigens Class I D018476:Hypokinesia D007276:Injections, Intraventricular D015227:Lipid Peroxidation D008297:Male D051379:Mice D053580:Muscle Strength D016627:Oxidopamine D010446:Peptide Fragments D011341:Probucol D011597:Psychomotor Performance D017392:Thiobarbituric Acid Reactive Substances
6-Hydroxidopamine Bradykinesia Hypokinesia Locomotor activity Parkinson’s disease Single pellet test