title: Central cholinergic depletion induced by 192 IgG-saporin alleviates the sedative effects of propofol in rats.
abstract: We examined the effect of central cholinergic depletion on the sedative potency of propofol in rats. Depletion was produced by intracerebroventricular administration of an immunotoxin specific to cholinergic neurones (192 IgG-Saporin; 2 microg). As a result of this lesion, acetylcholine concentration was reduced by about 40% in the frontoparietal cortex and in the hippocampus but was essentially normal in the striatum and cerebellum. Sedation in rats was assessed as the decrease in locomotor activity. Sedative potency of propofol (30 mg kg(-1) i.p.) was reduced by about 50% in rats who received the injection of 192 IgG-Saporin as compared to controls. These results show that a central cholinergic depletion alleviates the sedative effect of propofol, and indicates that basal forebrain cholinergic neurones might mediate part of the sedative/hypnotic effects of propofol.
authors.affiliation: GRERCA, U405 INSERM et Service d'Anesthesie, CHU Hautepierre, Strasbourg, France.
authors.forename: L
authors.initials: L
authors.lastname: Pain
authors.forename: H
authors.initials: H
authors.lastname: Jeltsch
authors.forename: O
authors.initials: O
authors.lastname: Lehmann
authors.forename: C
authors.initials: C
authors.lastname: Lazarus
authors.forename: F Z
authors.initials: FZ
authors.lastname: Laalou
authors.forename: J C
authors.initials: JC
authors.lastname: Cassel
mesh_terms: D000109:Acetylcholine / Q000032:analysis / Q000502:physiology; D018686:Anesthetics, Intravenous / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects*; D001923:Brain Chemistry; D018678:Cholinergic Agents / Q000494:pharmacology*; D002799:Cholinergic Fibers / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology; D005260:Female; D000922:Immunotoxins / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D009699:N-Glycosyl Hydrolases; D015742:Propofol / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins
chemical_list: C085696:192 IgG-saporin; D018686:Anesthetics, Intravenous; D000911:Antibodies, Monoclonal; D018678:Cholinergic Agents; D000922:Immunotoxins; D054789:Ribosome Inactivating Proteins, Type 1; D009699:N-Glycosyl Hydrolases; D000076985:Saporins; D000109:Acetylcholine; D015742:Propofol