Time-course of nigrostriatal damage, basal ganglia metabolic changes and behavioural alterations following intrastriatal injection of 6-hydroxydopamine in the rat: New clues from an old model

Fabio Blandini, Giovanna Levandis, Eleonora Bazzini, Giuseppe Nappi, Marie Therese Armentero

Research output: Contribution to journalArticle

Abstract

Despite the progressive development of innovative animal models for Parkinson's disease, the intracerebral infusion of neurotoxin 6-hydroxydopamine (6-OHDA) remains the most widely used means to induce an experimental lesion of the nigrostriatal pathway in the animal, due to its relatively low complexity and cost, coupled with the high reproducibility of the lesion obtained. To gain new information from such a classic model, we studied the time-course of the nigrostriatal damage, metabolic changes in the basal ganglia nuclei (cytochrome oxidase activity) and behavioural modifications (rotational response to apomorphine) following unilateral injection of 6-OHDA into the corpus striatum of rat, over a 4-week period. Striatal infusion of 6-OHDA caused early damage of dopaminergic terminals, followed by a slowly evolving loss of dopaminergic cell bodies in the substantia nigra pars compacta, which became apparent during the second week post-injection and peaked at the 28th day post-infusion; the rotational response to apomorphine was already present at the first time point considered (Day 1), and remained substantially stable throughout the 4-week period of observation. The evolution of the nigrostriatal lesion was accompanied by complex changes in the metabolic activity of the other basal ganglia nuclei investigated (substantia nigra pars reticulata, entopeduncular nucleus, globus pallidus and subthalamic nucleus), which led, ultimately, to a generalized, metabolic hyperactivity, ipsilaterally to the lesion. However, peculiar patterns of metabolic activation, or inhibition, characterized the post-lesional responses of each nucleus, in the early and intermediate phases, with peculiar response profiles that varied closely related to the functional position occupied within the basal ganglia circuitry.

Original languageEnglish
Pages (from-to)397-405
Number of pages9
JournalEuropean Journal of Neuroscience
Volume25
Issue number2
DOIs
Publication statusPublished - Jan 2007

Fingerprint

Oxidopamine
Basal Ganglia
Injections
Corpus Striatum
Apomorphine
Entopeduncular Nucleus
Subthalamic Nucleus
Globus Pallidus
Neurotoxins
Electron Transport Complex IV
Parkinson Disease
Animal Models
Observation
Costs and Cost Analysis

Keywords

  • Apomorphine
  • Cytochrome oxidase
  • Parkinson's disease
  • Striatum
  • Substantia nigra

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Time-course of nigrostriatal damage, basal ganglia metabolic changes and behavioural alterations following intrastriatal injection of 6-hydroxydopamine in the rat : New clues from an old model. / Blandini, Fabio; Levandis, Giovanna; Bazzini, Eleonora; Nappi, Giuseppe; Armentero, Marie Therese.

In: European Journal of Neuroscience, Vol. 25, No. 2, 01.2007, p. 397-405.

Research output: Contribution to journalArticle

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