Nigrostriatal damage with 6-OHDA validation of routinely applied procedures

Federica Fulceri, Francesca Biagioni, Paola Lenzi, Alessandra Falleni, Marco Gesi, Stefano Ruggieri, Francesco Fornai

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

The 6-hydroxydopamine (6-OHDA) model of Parkinson's disease in the rat represents a fundamental tool for investigating the pathophysiology of dopamine denervation. Nevertheless, 6-OHDA can induce also noradrenergic lesions; therefore desmethylimipramine (DMI) is co-administrated as a selective inhibitor of noradrenergic reuptake to protect noradrenaline (NA) fibers neighboring DA neurons and/or axons. The neurotoxin 6-OHDA must be microinfused selectively into the substantia nigra pars compacta (SNpc) or into the medial forebrain bundle (MFB) to determine the nigrostriatal lesion. However, this experimental procedure is invasive and always produces a certain amount of mechanical damage that cannot be prevented by pharmacological approaches. For this reason, we have compared two types of experimental design in which we tested critical steps of the procedures, such as the flow rate. We microinfused rats in MFB with 8 μL of total volume of a solution containing the neurotoxin (infusion rate 2 μL/min in 4 min) according with general practice, and rats microinfused with an amount of 2μL of total volume with a slower rate (0.2 μL/min in 10 min) of infusion. Rats infused with a higher flow rate of infusion underwent striatal NA loss in spite of the administration of DMI. On the contrary, rats infused with a slow infusion flow rate had spared NA axons following DMI. These results suggest that the flow rate and the volume of 6-OHDA infusion are critical to prevent the occurrence of nonspecific mechanical effects.

Original languageEnglish
Title of host publicationAnnals of the New York Academy of Sciences
Pages344-348
Number of pages5
Volume1074
DOIs
Publication statusPublished - Aug 2006

Publication series

NameAnnals of the New York Academy of Sciences
Volume1074
ISSN (Print)00778923
ISSN (Electronic)17496632

Keywords

  • 6-hydroxydopamine
  • Nigrostriatal pathway
  • Parkinson's disease

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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