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 2 h 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 2 h after training. In experiment 2, administration of LiCl (100 mg/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.

Research highlights
► Sevoflurane anesthesia impairs memory consolidation.
► Sevoflurane inhibits the training-associated enhancement of phosphorylation state of GSK-3β in the hippocampus.
► Sevoflurane-induced impairment of memory consolidation seems to be mediated by phosphorylation of GSK-3β modulation.