Forced limb-use effects on the behavioral and neurochemical effects of 6-hydroxydopamine.
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.
Tillerson
J L
JL
Institute for Neuroscience and the Division of Pharmacology and Toxicology, University of Texas at Austin, Austin, Texas 78712, USA. tillerson@psy.utexas.edu
Cohen
A D
AD
Philhower
J
J
Miller
G W
GW
Zigmond
M J
MJ
Schallert
T
T
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D001831:Body Temperature; D002370:Casts, Surgical; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects / Q000503:physiopathology*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D005552:Forelimb / Q000502:physiology; D006719:Homovanillic Acid / Q000378:metabolism; D007103:Immobilization; D008297:Male; D008474:Medial Forebrain Bundle / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000378:metabolism; D026901:Membrane Transport Proteins; D008845:Microinjections; D009434:Neural Pathways / Q000187:drug effects / Q000503:physiopathology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009479:Neuropeptides; D016627:Oxidopamine / Q000008:administration & dosage; D010300:Parkinson Disease / Q000503:physiopathology* / Q000517:prevention & control; D010302:Parkinson Disease, Secondary / Q000139:chemically induced; D051381:Rats; D020318:Rats, Long-Evans; D013378:Substantia Nigra / Q000187:drug effects / Q000503:physiopathology; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins
D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009479:Neuropeptides; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins; D015102:3,4-Dihydroxyphenylacetic Acid; D016627:Oxidopamine; D001058:Apomorphine; D004298:Dopamine; D006719:Homovanillic Acid