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

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 GABAA-receptors. The aim of the present study is to investigate a putative GABAB-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 GABAB-receptor antagonist CGP 35348 (200 mg/kg, i.v.) but not by pretreatment with the GABAA-receptor antagonist picrotoxin (4.5 mg/kg, i.v.).It is proposed that an activation of central GABAB-receptors may, at least partially, contribute to the anesthetic properties of propofol. [Copyright &y& Elsevier]