Dopamine receptor agonists mediate neuroprotection in malonate-induced striatal lesion in the rat

Marie Thérèse Armentero, Roberto Fancellu, Giuseppe Nappi, Fabio Blandini

Research output: Contribution to journalArticlepeer-review

Abstract

Mitochondrial bioenergetic defects are involved in neurological disorders associated with neuronal damage in the striatum, such as Huntington's disease and cerebral ischemia. The striatal release of neurotransmitters, in particular dopamine, may contribute to the development of the neuronal damage. Recent studies have shown that dopamine agonists may exert neuroprotective effects via multiple mechanisms, including modulation of dopamine release from nigrostriatal dopaminergic terminals. In rats, intrastriatal injection of malonate, a reversible inhibitor of the mitochondrial enzyme succinate dehydrogenase, induces a lesion similar to that observed following focal ischemia or in Huntington's disease. In this study, we used the malonate model to explore the neuroprotective potential of dopamine agonists. Sprague-Dawley rats were injected systemically with increasing concentrations of D1, D2, or mixed D1/D2 dopamine agonists prior to malonate intrastriatal insult. Administration of increasing doses of the D2-specific agonist quinpirole resulted in increased protection against malonate toxicity. Conversely, the D1-specific agonist SKF-38393, as well as the mixed D1/D2 agonist apomorphine, conferred higher neuroprotection at lower than at higher concentrations. Our data suggest that malonate-induced striatal toxicity can be attenuated by systemic administration of dopamine agonists, with D1 and D2 agonists showing different profiles of efficacy.

Original languageEnglish
Pages (from-to)301-305
Number of pages5
JournalExperimental Neurology
Volume178
Issue number2
DOIs
Publication statusPublished - 2002

Keywords

  • Apomorphine
  • Basal ganglia
  • Cytochrome oxidase
  • Quinpirole
  • SKF-38393
  • Striatum

ASJC Scopus subject areas

  • Neurology
  • Neuroscience(all)

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