Activation of nigral dopamine neurons by the selective GABA(B)-receptor antagonist SCH 50911

J Neural Transm (Vienna). 1999;106(5-6):383-94. doi: 10.1007/s007020050166.

Abstract

Previous studies have shown that systemic as well as local administration of the GABA(B)-receptor agonist baclofen is associated with a decrease in firing rate, a regularisation of firing rhythm and a decrease in burst firing activity of dopamine (DA) containing midbrain neurons. In the present electrophysiological study we have utilised the novel, selective and potent GABA(B)-receptor antagonist SCH 50911 in order to further analyse the importance of GABA(B)-receptors for the overall activity of rat nigral DA neurons. SCH 50911 given intravenously (1-64 mg/kg) or locally, by microiontophoretic techniques, was found to increase firing rate and to increase the burst firing activity of DA neurons. The present data suggest that the GABA(B)-receptor antagonist blocks somatodendritic receptors on nigral DA neurons. This GABA-receptor input appears to be of a tonic nature. It is proposed that the activation of nigral DA neurons may underlie the beneficial effects of GABA(B)-receptor antagonists in the modulation of cognition and that GABA(B)-receptor antagonists may be of therapeutic value in the treatment of Parkinson's disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Baclofen / pharmacology
  • Dendrites / drug effects
  • Dendrites / physiology
  • Dopamine / physiology*
  • Electrophysiology
  • GABA Antagonists / pharmacology*
  • GABA-B Receptor Antagonists*
  • Kinetics
  • Kynurenic Acid / pharmacology
  • Male
  • Microelectrodes
  • Morpholines / pharmacology*
  • Muscimol / pharmacology
  • Neurons / drug effects
  • Neurons / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Substantia Nigra / drug effects
  • Substantia Nigra / physiology*
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology

Substances

  • (+)-(S)-5,5-dimethylmorpholinyl-2-acetic acid
  • GABA Antagonists
  • GABA-B Receptor Antagonists
  • Morpholines
  • Muscimol
  • Kynurenic Acid
  • Baclofen
  • Dopamine