The anaesthetic agent propofol interacts with GABA(B)-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 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.
Schwieler
L
L
Department of Physiology and Pharmacology, Karolinska Institute, 171 77, Stockholm, Sweden.
Delbro
D S
DS
Engberg
G
G
Erhardt
S
S
D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005110:Extracellular Space / Q000187:drug effects / Q000502:physiology; D018756:GABA Antagonists / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000187:drug effects; D009943:Organophosphorus Compounds / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010852:Picrotoxin / Q000494:pharmacology; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018080:Receptors, GABA-B / Q000187:drug effects*; D013378:Substantia Nigra / Q000187:drug effects
D018686:Anesthetics, Intravenous; D018756:GABA Antagonists; D009943:Organophosphorus Compounds; D010852:Picrotoxin; D015742:Propofol; D018080:Receptors, GABA-B; C066430:CGP 35348