Presynaptic dopamine D2-like receptors inhibit excitatory transmission onto rat ventral tegmental dopaminergic neurones

J Physiol. 2000 Feb 15;523 Pt 1(Pt 1):163-73. doi: 10.1111/j.1469-7793.2000.t01-2-00163.x.

Abstract

1. The effects of dopamine (DA) on non-NMDA glutamatergic transmission onto dopaminergic neurones in the ventral tegmental area (VTA) were examined in rat midbrain slices using the whole-cell patch-clamp technique. EPSCs in dopaminergic neurones evoked by focal stimulation within the VTA were reversibly blocked by 5 microM CNQX in the presence of bicuculline (20 microM), strychnine (0.5 microM) and D-amino-5-phosphonopentanoic acid (D-AP5, 25 microM). 2. Bath application of DA reduced the amplitude of EPSCs up to 65.1 +/- 9. 52% in a concentration-dependent manner between 0.3-1000 microM (IC50, 16.0 microM) without affecting the holding current at -60 mV measured using a Cs+-filled electrode. 3. The effect of DA on evoked EPSCs was mimicked by the D2-like receptor agonist quinpirole but not by the D1-like receptor agonist SKF 81297, and was antagonized by the D2-like receptor antagonist sulpiride (KB, 0.96 microM), but not by the D1-like receptor antagonist SCH 23390 (KB, 228.6 microM). 4. Dopamine (30 microM) reduced the mean frequency of spontaneous miniature EPSCs (mEPSCs) without affecting their mean amplitude, and the DA-induced effect on the mEPSCs was dependent on the external Ca2+ concentration. 5. These results suggest that afferent glutamatergic fibres which terminate on VTA dopaminergic neurones possess presynaptic D2-like receptors, activation of which inhibits glutamate release by reducing Ca2+ influx.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dopamine / metabolism*
  • Dopamine / pharmacology
  • Dopamine Agonists / pharmacology
  • Dopamine Antagonists / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology
  • Neural Inhibition / physiology*
  • Neurons / metabolism
  • Neurons / physiology
  • Presynaptic Terminals / metabolism*
  • Rats
  • Receptors, Dopamine D2 / physiology*
  • Synaptic Transmission / physiology*
  • Tegmentum Mesencephali / cytology
  • Tegmentum Mesencephali / physiology*

Substances

  • Dopamine Agonists
  • Dopamine Antagonists
  • Receptors, Dopamine D2
  • Dopamine