Norepinephrine loss selectively enhances chronic nigrostriatal dopamine depletion in mice and rats

Francesco Fornai, Maria Tilde Torracca, Lucia Bassi, Daniela Anna D'Errigo, Vera Scalori, Giovanni U. Corsini

Research output: Contribution to journalArticlepeer-review


In this study we investigated whether a selective pattern of norepinephrine loss potentiates methamphetamine-induced striatal dopamine depletion in rats. We also evaluated whether chronic norepinephrine depletion reduces the threshold dose of methamphetamine necessary to induce long-lasting striatal dopamine loss in mice and in rats. Pre-treatment with the selective noradrenergic neurotoxin DSP-4 (50 mg/kg, i.p.) in mice and in rats significantly enhanced methamphetamine-induced striatal dopamine depletion. Administration of a low dose of methamphetamine (1 x 5 mg/kg and 3 x 5 mg/kg, respectively, i.p., at 2-h interval) to C57B1/6N mice and Sprague-Dawley rats did not decrease striatal dopamine levels when injected alone but produced a significant decrease in striatal dopamine when given to rodents carrying a long-lasting norepinephrine depletion previously induced by DSP-4. Our results suggest that norepinephrine loss might both enhance neurotoxic damage and decrease the threshold for neurotoxicity to nigrostriatal dopaminergic neurons in different animal species.

Original languageEnglish
Pages (from-to)349-353
Number of pages5
JournalBrain Research
Issue number2
Publication statusPublished - Oct 7 1996


  • Dopamine
  • DSP-4
  • Methamphetamine
  • Neurotoxic threshold
  • Nigrostriatal pathway
  • Norepinephrine

ASJC Scopus subject areas

  • Neuroscience(all)

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