Sevoflurane attenuates stress-enhanced fear learning by regulating hippocampal BDNF expression and Akt/GSK-3β signaling pathway in a rat model of post-traumatic stress disorder.

Abstract

Post-traumatic stress disorder (PTSD) is a psychiatric disease that may occur after intense psychological trauma or physiological stress. Accumulating evidence suggests that brain-derived neurotrophic factor (BDNF) and the serine/threonine kinase (Akt)/glycogen synthase kinase-3β (GSK-3β) signaling pathway are critically involved in brain plasticity, including hippocampal-dependent learning and memory, while sevoflurane impairs memory processing. Thus, we hypothesized that sevoflurane can suppress fear learning by regulating the expression of BDNF and the Akt/GSK-3β signaling pathway in a rat model of PTSD. Rats were exposed to sevoflurane during or after a 15 foot-shock stressor. Thereafter, rats were subjected to a single foot-shock in a totally different environment. The fear response was recorded in response to the 15 foot-shock and the single foot-shock environments. In another set of experiments, the brain tissue was harvested and subjected to biochemistry studies. Our data suggested that increasing sevoflurane concentrations decreased stress-enhanced fear learning (SEFL) when given during but not after the stressor. Furthermore, administration of lithium chloride (100 mg/kg, intraperitoneally) 30 min before the contextual fear conditioning reversed the inhibitory effect of 0.8 % sevoflurane on SEFL as well as phosphorylated (p)-Akt, p-GSK-3β and BDNF expressions. Our data suggested that increasing sevoflurane administration during but not after the stressor can impair SEFL in a rat model of PTSD, which may be due, at least in part, to the regulation of hippocampal BDNF expression and the Akt/GSK-3β signaling pathway.