Forced Limb-Use Effects on the Behavioral and Neurochemical Effects of 6-Hydroxydopamine

Abstract

Rats with unilateral depletion of striatal dopamine (DA) show marked preferential use of the ipsilateral forelimb. Previous studies have shown that implementation of motor therapy after stroke improves functional outcome (Taub et al., 1999). Thus, we have examined the impact of forced use of the impaired forelimb during or soon after unilateral exposure to the DA neurotoxin 6-hydroxydopamine (6-OHDA). In one group of animals, the nonimpaired forelimb was immobilized using a cast, which forced exclusive use of the impaired limb for the first 7 d after infusion. The animals that received a cast displayed no detectable impairment or asymmetry of limb use, could use the contralateral (impaired) forelimb independently for vertical and lateral weight shifting, and showed no contralateral turning to apomorphine. The behavioral effects were maintained throughout the 60 d of observation. In addition to the behavioral sparing, these animals showed remarkable sparing of striatal DA, its metabolites, and the expression of the vesicular monoamine transporter, suggesting a decrease in the extent of DA neuron degeneration. Behavioral and neurochemical sparing appeared to be complete when the 7 d period of immobilization was initiated immediately after 6-OHDA infusion, only partial sparing was evident when immobilization was initiated 3 d postoperatively, and no sparing was detected when immobilization was initiated 7 d after 6-OHDA treatment. These results suggest that physical therapy may be beneficial in Parkinson's disease.

The Nociceptin/Orphanin FQ Receptor Antagonist J-113397 and l-DOPA Additively Attenuate Experimental Parkinsonism through Overinhibition of the Nigrothalamic Pathway

“…The bar test essentially measures the time to initiate a movement (akinesia), whereas the drag test measures both the time to initiate and to execute it (bradykinesia). The degree of motor asymmetry in the drag test (ϳ65%) was consistent with that reported by Wessell et al (2004) (ϳ75%) and in line with that found with the stepping [ϳ90% (Olsson et al, 1995); 80 -90% (Winkler et al, 2002); ϳ70% (Tillerson et al, 2001); ϳ75% (Tseng et al, 2005); 50 -90% (Kelsey et al, 2004)] or the postural adjustment [ϳ75% (Lindner et al, 1996); Ͼ95% (Chang et al, 1999)] tests. Powerful, dose-dependent attenuation of parkinsonism was produced by increasing L-DOPA doses: reduction of akinesia at both the ipsilateral and the contralateral forepaw (0.1 mg/kg), improvement of exercise-induced motor performance (0.3 mg/kg), and reversal of motor asymmetry both under resting (bar test) and dynamic (drag test) conditions (6 mg/kg).…”

Behavioral tests for preclinical intervention assessment

“…The use of each forelimb for weight support or weight shifting along the walls is examined using slow motion video recordings. [21][22][23][24] An experienced investigator can accurately score the data live, however. The test is sensitive to long-term deficits in forelimb use that might otherwise be masked by motor learning, and the scores do not change with repeated testing.…”

The effect of thrombin on a 6-hydroxydopamine model of Parkinson's disease depends on timing

“…Vibrissae-elicited forelimb placing (placing test)-This test has been well described and utilized to measure 6-OHDA-elicited deficits [35,39,44]. Additionally, thrombin preconditioning has been found to provide protection from 6-OHDA-elicited deficits in this test [3].…”

“…utilized to assess 6-OHDA-elicited deficits [35,39] and also protection elicited by preconditioning in this model [3,39]. Briefly, the animal was placed in a clear plastic cylinder (height: 30 cm, width: 20 cm) and forelimb asymmetry was determined during rearing behavior.…”