Role of endogenous melatonin in the oxidative homeostasis of the extracellular striatal compartment: A microdialysis study in PC12 cells in vitro and in the striatum of freely moving rats

Gaia Rocchitta, Rossana Migheli, Maria P. Mura, Giovanni Esposito, Bianca Marchetti, Maria S. Desole, Egidio Miele, Pier Andrea Serra

Research output: Contribution to journalArticle


A capillary apparatus for in vitro microdialysis was used to investigate melatonin and ascorbic acid effects on dopamine (DA) autoxidation or nitric oxide (NO)-mediated oxidation in suspended PC12 cells. Following high K + (KCl 75 mm) infusion, secreted DA underwent a partial autoxidation or peroxynitrite-mediated oxidation when the potential peroxynitrite generator q13-morpholinosydnonimine (SIN-1, 1.0 mm) was co-infused with KCl. Ascorbic acid was supplied to the medium by means of intracellular reduction of infused dehydroascorbic acid (DHAA) (5.0 mm). Melatonin (50 μm) and DHAA showed a synergistic effect in inhibiting DA autoxidation and peroxynitrite-mediated DA oxidation. Moreover, melatonin increased dialysate recovery of ascorbic acid released from PC12 cells. Endogenous melatonin was depleted in rats maintained on a 24-hr light cycle for 1 wk. In melatonin-depleted rats, baseline levels of dialysate ascorbic acid were lower than controls, while those of DA were unaffected. In these rats, intrastriatal infusion of 5.0 mm SIN-1 induced DA increases significantly lower than in controls; in addition, dialysate ascorbic acid concentrations exhibited significant decreases. Melatonin co-infusion restored SIN-1 effects on dialysate DA and antagonized SIN-1-induced ascorbic acid decreases. Melatonin-depleted rats were allowed to recover. In these rats, striatal baseline ascorbic acid, as well as SIN-1-induced increases in dialysate DA did not differ from controls. Taken together, these findings suggest that endogenous melatonin is an active component of the striatal extracellular antioxidant pool, as it maintains endogenous ascorbic acid in its reduced status and co-operates with ascorbic acid in protecting extracellular DA from exogenous NO-mediated oxidation.

Original languageEnglish
Pages (from-to)409-418
Number of pages10
JournalJournal of Pineal Research
Issue number4
Publication statusPublished - Nov 2005



  • Ascorbic acid
  • Endogenous melatonin
  • Extracellular oxidation
  • Nitric oxide
  • Striatal dopamine

ASJC Scopus subject areas

  • Endocrinology

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