Involvement of the basal cholinergic forebrain in the mediation of general (propofol) anesthesia.
BACKGROUND
Recent studies have pointed out the involvement of the basal forebrain gamma-aminobutyric acid-mediated system in mediating the effects of general anesthesia. In this study, the authors asked whether the basal forebrain cholinergic system is also involved in mediating the effects of general anesthetics such as propofol.


METHODS
Cholinergic lesions were produced by administration of the selective immunotoxin 192 immunoglobulin G-saporin into the lateral ventricles, the medial septum, or the nucleus basalis magnocellularis. The anesthetic potency of propofol was determined using an anesthetic score with a crossover counterbalanced design. Animals were given intraperitoneal propofol (25 or 50 mg/kg) repeatedly every 15 min to set up a subanesthetic (low-dose) or anesthetic (high-dose) state. The anesthetic score was assessed for each cumulative dose. Control of the cholinergic depletion was performed using histochemical acetylcholinesterase staining on brain slices.


RESULTS
A shift from a subanesthetic state to an anesthetic state was observed mainly in the rats with the immunotoxin injected into the lateral ventricles or the medial septum and vertical diagonal band of Broca, compared with controls. In those rats, the density of acetylcholinesterase reaction products was normal in the striatum and the thalamus, but reduced in the cortex and the hippocampus.


CONCLUSIONS
The anesthetic potency of propofol was increased in all rats with hippocampal lesions, whatever the injection sites, compared with controls. These results demonstrate that a cholinergic dysfunction in the basal forebrain potentiates the anesthetic effects of propofol.
Laalou
Fatem-Zohra
FZ
Groupe de Recherche Expérimentale sur les Répercussions Cognitivo-affectives de l'anesthésie, Inserm U666, France.
de Vasconcelos
Anne Pereira
AP
Oberling
Philippe
P
Jeltsch
Hélène
H
Cassel
Jean-Christophe
JC
Pain
Laure
L
D018686:Anesthetics, Intravenous / Q000494:pharmacology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000633:toxicity; D020532:Basal Nucleus of Meynert / Q000187:drug effects / Q000502:physiology*; D020667:Diagonal Band of Broca / Q000187:drug effects / Q000502:physiology; D000922:Immunotoxins / Q000008:administration & dosage / Q000633:toxicity; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D008297:Male; D015742:Propofol / Q000008:administration & dosage / Q000494:pharmacology*; D016548:Prosencephalon / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D020318:Rats, Long-Evans; D054789:Ribosome Inactivating Proteins, Type 1 / Q000008:administration & dosage / Q000633:toxicity; D000076985:Saporins
C085696:192 IgG-saporin; D018686:Anesthetics, Intravenous; D000911:Antibodies, Monoclonal; D000922:Immunotoxins; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D015742:Propofol