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

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.