Neuroprotective effects of prior limb use in 6-hydroxydopamine-treated rats: possible role of GDNF

J Neurochem. 2003 Apr;85(2):299-305. doi: 10.1046/j.1471-4159.2003.01657.x.


Unilateral administration of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle (MFB) causes a loss of dopamine (DA) in the ipsilateral striatum and contralateral motor deficits. However, if a cast is placed on the ipsilateral limb during the first 7 days following 6-OHDA infusion, forcing the animal to use its contralateral limb, both the behavioral and neurochemical deficits are reduced. Here, we examine the effect of forced reliance on a forelimb during the 7 days prior to ipsilateral infusion of 6-OHDA on the deficits characteristic of this lesion model. Casted animals displayed no behavioral asymmetries as measured 14-28 days postlesion and a marked attenuation in the loss of striatal DA and its metabolites at 30 days. In addition, animals receiving a unilateral cast alone had an increase in glial cell-line derived neurotrophic factor (GDNF) protein in the striatum corresponding to the overused limb. GDNF increased within 1 day after the onset of casting, peaked at 3 days, and returned to baseline within 7 days. These results suggest that preinjury forced limb-use can prevent the behavioral and neurochemical deficits to the subsequent administration of 6-OHDA and that this may be due in part to neuroprotective effects of GDNF.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3,4-Dihydroxyphenylacetic Acid / metabolism
  • Animals
  • Apomorphine / pharmacology
  • Behavior, Animal / drug effects
  • Casts, Surgical
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism
  • Disease Models, Animal
  • Dopamine / metabolism
  • Forelimb* / physiopathology
  • Functional Laterality
  • Glial Cell Line-Derived Neurotrophic Factor
  • Immobilization / physiology
  • Male
  • Medial Forebrain Bundle / drug effects*
  • Motor Activity / drug effects
  • Nerve Growth Factors / metabolism*
  • Oxidopamine / administration & dosage
  • Oxidopamine / pharmacology*
  • Parkinson Disease, Secondary / chemically induced
  • Parkinson Disease, Secondary / physiopathology*
  • Parkinson Disease, Secondary / prevention & control
  • Rats
  • Rats, Long-Evans
  • Rats, Sprague-Dawley


  • Gdnf protein, rat
  • Glial Cell Line-Derived Neurotrophic Factor
  • Nerve Growth Factors
  • 3,4-Dihydroxyphenylacetic Acid
  • Oxidopamine
  • Apomorphine
  • Dopamine