Characterization of behavioral and neurodegenerative changes following partial lesions of the nigrostriatal dopamine system induced by intrastriatal 6-hydroxydopamine in the rat

Exp Neurol. 1998 Aug;152(2):259-77. doi: 10.1006/exnr.1998.6848.


Partial lesions of the nigrostriatal dopamine system have been investigated with respect to their ability to induce consistent long-lasting deficits in movement initiation and skilled forelimb use. In eight different lesion groups 6-hydroxydopamine (6-OHDA) was injected at one, two, three, or four sites into the lateral sector of the right striatum, in a total dose of 20-30 microgram. Impairments in movement initiation in a forelimb stepping test, and in skilled paw use in a paw-reaching test, was seen only in animals where the severity of the lesion exceeded a critical threshold, which was different for the different tests used: single (1 x 20 microgram) or two-site (2 x 10 microgram) injections into the striatum had only small affects on forelimb stepping, no effect on skilled paw use. More pronounced deficits were obtained in animals where the same total dose of 6-OHDA was distributed over three or four sites along the rostro-caudal extent of the lateral striatum or where the injections were made close to the junction of the globus pallidus. The results show that a 60-70% reduction in tyrosine hydroxylase (TH)-positive fiber density in the lateral striatum, accompanied by a 50-60% reduction in TH-positive cells in substantia nigra (SN), is sufficient for the induction of significant impairment in initiation of stepping. Impaired skilled paw-use, on the other hand, was obtained only with a four-site (4 x 7 microgram) lesion, which induced 80-95% reduction in TH fiber density throughout the rostrocaudal extent of the lateral striatum and a 75% loss of TH-positive neurons in SN. Drug-induced rotation, by contrast, was observed also in animals with more restricted presymptomatic lesions. The results indicate that the four-site intrastriatal 6-OHDA lesion may be a relevant model of the neuropathology seen in parkinsonian patients in a manifest symptomatic stage of the disease and may be particularly useful experimentally since it leaves a significant portion of the nigrostriatal projection intact which can serve as a substrate for regeneration and functional recovery in response to growth promoting and neuroprotective agents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amphetamine / pharmacology
  • Animals
  • Apomorphine / pharmacology
  • Corpus Striatum / physiology*
  • Dopamine / physiology*
  • Female
  • Forelimb / innervation
  • Microinjections
  • Motor Activity / drug effects
  • Motor Activity / physiology*
  • Nerve Degeneration / physiopathology*
  • Neurons / enzymology
  • Oxidopamine
  • Psychomotor Performance / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Rotation
  • Substantia Nigra / physiology*
  • Tyrosine 3-Monooxygenase / analysis


  • Oxidopamine
  • Amphetamine
  • Tyrosine 3-Monooxygenase
  • Apomorphine
  • Dopamine