The septohippocampal system participates in general anesthesia.
How the brain mediates general anesthesia is not known. We report that two interconnected structures in the forebrain, the medial septum and the hippocampus, participate in maintaining awareness and movements during general anesthesia. In the awake, freely behaving rat, inactivation of the medial septum or the hippocampus by local injection of a GABA(A) receptor agonist, muscimol, decreased the dose of a general anesthetic needed to induce a loss of the tail-pinch response or a loss of righting reflex. Septohippocampal inactivation also suppressed the behavioral hyperactivity or the delirium stage associated with general anesthesia. An increase and decrease of 30-50 Hz (gamma) waves in the hippocampus correlated with an increase and decrease in behavioral activity, respectively. Similar results were found for both volatile (halothane and isoflurane) and nonvolatile (propofol and pentobarbital) anesthetics. We conclude that the behavioral hyperactivity induced by a general anesthetic is mediated in part by the septohippocampal system, and that depression of the septohippocampal system increases the potency of a general anesthetic. It is suggested that more potent general anesthetics or adjuvants may be developed by maximizing the pharmacological depression of the septohippocampal system.
Ma
Jingyi
J
Department of Physiology, University of Western Ontario, London, Ontario, Canada N6A 5A5.
Shen
Bixia
B
Stewart
Lee S
LS
Herrick
Ian A
IA
Leung
L Stan
LS
D000758:Anesthesia; D018681:Anesthetics, General / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D004569:Electroencephalography; D018755:GABA Agonists / Q000008:administration & dosage; D058785:GABA-A Receptor Agonists; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology*; D006948:Hyperkinesis / Q000139:chemically induced; D008297:Male; D008845:Microinjections; D009068:Movement / Q000187:drug effects / Q000502:physiology; D009118:Muscimol / Q000008:administration & dosage; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D020318:Rats, Long-Evans; D012018:Reflex / Q000187:drug effects / Q000502:physiology; D020665:Septum of Brain / Q000187:drug effects* / Q000502:physiology*
D018681:Anesthetics, General; D018755:GABA Agonists; D058785:GABA-A Receptor Agonists; D009118:Muscimol