The anaesthetic agent propofol interacts with GABA(B)-receptors: an electrophysiological study in rat

Life Sci. 2003 May 2;72(24):2793-801. doi: 10.1016/s0024-3205(03)00182-6.

Abstract

The mode of action by which propofol induces anaesthesia is not fully understood, although several studies suggest that the compound acts via potentiation of brain GABA(A)-receptors. The aim of the present study is to investigate a putative GABA(B)-receptor agonistic action of propofol. For this purpose the action of propofol on a GABA-receptor mediated regulation of dopamine neurons was analyzed with extracellular single unit recordings of dopaminergic neurons of the substantia nigra in chloral hydrate anaesthetized rats. Intravenous administration of propofol (1-16 mg/kg) was found to dose-dependently decrease the firing rate and burst firing activity of nigral DA neurons. These effects by propofol were effectively antagonized by pretreatment with the selective GABA(B)-receptor antagonist CGP 35348 (200 mg/kg, i.v.) but not by pretreatment with the GABA(A)-receptor antagonist picrotoxin (4.5 mg/kg, i.v.). It is proposed that an activation of central GABA(B)-receptors may, at least partially, contribute to the anesthetic properties of propofol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anesthetics, Intravenous / pharmacology*
  • Animals
  • Dose-Response Relationship, Drug
  • Electrophysiology
  • Extracellular Space / drug effects
  • Extracellular Space / physiology
  • GABA Antagonists / pharmacology
  • Male
  • Neurons / drug effects
  • Organophosphorus Compounds / pharmacology
  • Patch-Clamp Techniques
  • Picrotoxin / pharmacology
  • Propofol / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, GABA-B / drug effects*
  • Substantia Nigra / drug effects

Substances

  • Anesthetics, Intravenous
  • GABA Antagonists
  • Organophosphorus Compounds
  • Receptors, GABA-B
  • Picrotoxin
  • CGP 35348
  • Propofol