Sevoflurane impairs memory consolidation in rats, possibly through inhibiting phosphorylation of glycogen synthase kinase-3β in the hippocampus.
Sevoflurane administration impairs memory processes in both humans and animals. Increasing evidence suggests that enhancement of the phosphorylation state of glycogen synthase kinase-3β (GSK-3β), as a result of acute administration of lithium chloride (LiCl), may enhance memory consolidation. The current experiments examined whether GSK-3β phosphorylation was involved in mediating the memory impairing effects of posttraining sevoflurane on inhibitory avoidance (IA) retention. In experiment 1, adult male Sprague-Dawley rats were exposed to sevoflurane (0.5%, 1%, or 2%) for 2h immediately after training in a continuous multiple-trail IA paradigm. Sevoflurane (2% inspired) induced significant impairment of retention performance on a 24-h test and inhibited phosphorylation of GSK-3β in the hippocampus 2h after training. In experiment 2, administration of LiCl (100mg/kg, intraperitoneally) 30 min before IA training not only blocked the sevoflurane-induced impairment of consolidation, but also reversed the inhibitory effect of sevoflurane on GSK-3β phosphorylation in the hippocampus. Collectively, these findings support the hypothesis that sevoflurane exposure can impair consolidation of IA memory in rats. Sevoflurane-induced amnesia may be due, at least in part, to suppression of GSK-3β phosphorylation in the hippocampus.
Liu
Xue-Sheng
XS
Department of Anesthesiology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200025, PR China.
Xue
Qing-sheng
QS
Zeng
Qing-Wen
QW
Li
Qian
Q
Liu
Jian
J
Feng
Xiao-Mei
XM
Yu
Bu-Wei
BW
D000704:Analysis of Variance; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D038362:Glycogen Synthase Kinase 3 / Q000187:drug effects / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006624:Hippocampus / Q000187:drug effects* / Q000201:enzymology; D018021:Lithium Chloride / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D008738:Methyl Ethers / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D000077149:Sevoflurane; D018709:Statistics, Nonparametric
D018685:Anesthetics, Inhalation; D004791:Enzyme Inhibitors; D008738:Methyl Ethers; D000077149:Sevoflurane; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D038362:Glycogen Synthase Kinase 3; D018021:Lithium Chloride