Presynaptic inhibition preferentially reduces the NMDA receptor-mediated component of transmission in rat midbrain dopamine neurons

Yan Na Wu, Ke Zhong Shen, Steven W. Johnson

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

1. We used patch pipettes to record whole-cell currents from single dopamine neurons in slices of rat midbrain. Pharmacological methods were used to isolate EPSCs evoked by focal electrical stimulation. 2. Baclofen was significantly more potent for inhibiting NMDA receptor-mediated EPSCs (IC50 = 0.24 μM) compared with inhibition of EPSCs mediated by AMPA receptors (IC50 = 1.72 μM). The increased potency of baclofen for inhibiting the NMDA component persisted in superfusate that contained zero Mg2+ and when postsynaptic K+ conductances were reduced by Cs+ and QX-314. Effects of baclofen on EPSCs were blocked by the GABA(B) receptor antagonist CGP-35348. 3. Adenosine was 20 fold more potent for reducing the NMDA component of transmission (IC50 = 31 μM) compared with inhibition of AMPA receptor-mediated EPSCs (IC50 = 654 μM). Effects of adenosine on EPSCs were blocked by the A1 receptor antagonist DPCPX. 4. Both baclofen and adenosine significantly increased the ratio of EPSCs in paired-pulse studies, suggesting presynaptic sites of action. Although adenosine (1 mM ) did not reduce currents evoked by exogenous NMDA (10 μM), baclofen (1 μM) reduced NMDA currents by 29%. Neither baclofen nor adenosine altered currents evoked by exogenous AMPA (1 μM). 5. We conclude that adenosine acts at presynaptic A1 receptors to cause a preferential reduction in the NMDA component of synaptic transmission. In contrast, baclofen preferentially reduces NMDA EPSCs by acting at both pre- and postsynaptic GABA(B) receptors. By regulating NMDA receptor function, A1 and GABA(B) receptors may play important roles in regulating the excitability of dopamine neurons.

Original languageEnglish (US)
Pages (from-to)1422-1430
Number of pages9
JournalBritish Journal of Pharmacology
Volume127
Issue number6
DOIs
StatePublished - 1999

Keywords

  • Adenosine
  • Baclofen
  • EPSC
  • GABA(B)
  • N-methyl-D-aspartate
  • Presynaptic inhibition
  • Substantia nigra
  • Synaptic transmission
  • Ventral tegmental area
  • Voltage-clamp

ASJC Scopus subject areas

  • Pharmacology

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