D2 autoreceptor inhibition reveals oxygen-glucose deprivation-induced release of dopamine in guinea-pig cochlea

G. Halmos, Z. Doleviczényi, G. Répássy, Á Kittel, E. S. Vizi, B. Lendvai, T. Zelles

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16 Citations (Scopus)

Abstract

Dopamine (DA), released from the lateral olivocochlear (LOC) efferent terminals, the efferent arm of the short-loop feedback in the cochlea, is considered as a protective factor in the inner ear since it inhibits auditory nerve dendrite firing in ischemia- or noise-induced excitotoxicity leading to sensorineural hearing loss (SNHL). In the present study we investigated the effect of oxygen-glucose deprivation (OGD), an in vitro ischemia model, on guinea-pig cochlear [3H]DA release in a microvolume superfusion system. We found that OGD alone failed to induce a detectable elevation of [3H]DA level, but in the presence of specific D2 receptor antagonists, sulpiride and L-741,626, it evoked a significant increase in the extracellular concentration of [3H]DA. D2 negative feedback receptors are involved not exclusively in the regulation of synthesis and vesicular release of DA, but also in the activation of its reuptake. Thus, D2 receptor antagonism interferes with the powerful reuptake of DA from the extracellular space. To explore the underlying mechanism of this DA-releasing effect we applied nomifensine and found that the effect of OGD on cochlear DA release in the presence of D2 antagonists could be inhibited by this selective DA uptake inhibitor. This finding indicates that the OGD-evoked DA release was mainly mediated through the reverse operation of the DA transporter. The two structurally different D2 antagonists also augmented the electrical field stimulation-evoked release of DA proving the presence of D2 autoreceptors on dopaminergic LOC terminals. Our results confirm the presence and role of D2 DA autoreceptors in the regulation of DA release from LOC efferents, and suggest a protective local mechanism during ischemia which involves the direct transporter-mediated release of DA. Increasing the release of the protective transmitter DA locally in the inner ear may form the basis of future new therapeutic strategies in patients suffering from SNHL.

Original languageEnglish
Pages (from-to)801-809
Number of pages9
JournalNeuroscience
Volume132
Issue number3
DOIs
Publication statusPublished - Jan 1 2005

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Keywords

  • Cochlea
  • D autoreceptor
  • Dopamine release
  • Ischemia
  • Oxygen-glucose deprivation
  • Transporter

ASJC Scopus subject areas

  • Neuroscience(all)

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