Group I metabotropic glutamate receptors activate burst firing in rat midbrain dopaminergic neurons

Simonetta Prisco, Silvia Natoli, Giorgio Bernardi, Nicola B. Mercuri

Research output: Contribution to journalArticle

Abstract

We have investigated the changes in the spontaneous firing pattern induced by DHPG ((S)-3,5-dihydroxyphenylglycine) and NMDA (N-methyl-d-aspartic acid) on rat dopaminergic neurons in substantia nigra pars compacta (SNc) using sharp microelectrode recordings in in vitro conditions. Twenty-five out of 33 cells modified the regular single-pacemaker activity in burst firing when exposed to the Group I metabotropic glutamate receptor (mGluR) agonist DHPG (30 μM) and d-tubocurarine (500 μM) (d-TC), whereas they all fired in bursts during NMDA (20 μM) plus d-TC application. The blockade of SK-channels by d-TC and apamin was essential for the production of both types of bursts. Although the two drugs induced a similar number of action potentials per burst, the DHPG-induced bursts had a lower frequency, a longer duration and a longer plateau period without spikes. In addition, the DHPG-induced bursting had a longer wash-out, could be reduced or blocked by the mGluR 1 selective, non-competitive antagonist CPCCOEt (7-cyclopropan[b]chromen-1a-carboxylic acid ethyl ester) (100 μM) while it was not affected by the mGluR 5 selective antagonist MPEP (2-methyl-6-(phenylethynyl)-pyridine (10 μM). These results suggest that both the activation of glutamate metabotropic type 1 and NMDA ionotropic receptors induce burst firing in the dopaminergic cells of the ventral midbrain when the activity of the SK-channels is reduced.

Original languageEnglish
Pages (from-to)289-296
Number of pages8
JournalNeuropharmacology
Volume42
Issue number3
DOIs
Publication statusPublished - 2002

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Keywords

  • Apamin
  • Bursts
  • d-tubocurarine
  • DHPG
  • Dopaminergic neurons
  • NMDA
  • Single-spike mode
  • SK-channels

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Drug Discovery
  • Pharmacology

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