Data are expressed as the mean SEM (n= 10 per group) and were analyzed by Tukey’s test after one-way analysis of variance

Data are expressed as the mean SEM (n= 10 per group) and were analyzed by Tukey’s test after one-way analysis of variance. subhypnotic propofol administration impairs memory retrieval and that the amnestic effects of propofol may be mediated by attenuated GSK-3 signaling in the hippocampus. == Introduction == Propofol, an alkylphenol derivative, is a commonly used intravenous anesthetic and sedative. Many pharmacological effects of propofol have been elucidated, JNJ-7706621 including sedative (Franks and Lieb, 1994; Jurd et al., 2003), antinociceptive (Guindon et al., 2007; Takechi et al., 2013) and organ-protecting (Andrews et al., 2012; Cui et al., 2013; Sahin et al., Bmp8b 2015) effects. Studies have also demonstrated effects of propofol on learning and memory, although there is some controversy about the nature of these effects. For example , subhypnotic doses of propofol have been shown to produce anterograde amnesia of inhibitory avoidance (Ren et al., 2008) and also to accelerate extinction of conditioned taste aversion (Ishitobi et al., 2003). By contrast, Hauer et al. (2011) reported that anesthetic doses of propofol enhance memory consolidationviathe endocannabinoid system. Memory function is complex but is classically divided into three distinct phases: encoding, consolidation, and retrieval (Abel and Lattal, 2001). Most previous studies examining the effects of propofol on memory were conducted with administration of JNJ-7706621 the drug shortly before or immediately after learning, thereby addressing effects on memory encoding and consolidation (Pain et al., 2002; Zhang et al., 2013). However , the effects of propofol on memory retrieval and retrieval-related mechanisms have not been addressed. Glycogen synthase kinase-3 (GSK-3) is a serine/threonine protein kinase. Phosphorylation of the serine-9 residue of GSK-3 inhibits the function JNJ-7706621 of the enzyme (Sutherland et al., 1993; Jung et al., 2015), whereas phosphorylation of its tyrosine-216 residue increases its activity (Hughes et al., 1993). Recent studies have suggested that the phosphorylating activity of GSK-3 plays a functional role in memory processes (Liu et al., 2003; Hooper et al., 2007). Constitutively active GSK-3 is required for memory retrieval, and memory JNJ-7706621 retrieval can be inhibited by intrahippocampal administration of the GSK-3 inhibitor SB216763 (Hong et al., 2012). The retrieval phase is required for development of long-term depression (Zhang et al., 2008). Propofol not only inhibits GSK-3 (Whittington et al., 2011) but also facilitates the development of long-term depression (Wei et al., 2002). These findings suggest that propofol may affect memory retrieval through modulation of GSK-3 activity. In the present study, we examined the hypothesis that propofol affects memory retrieval through an effect on GSK-3 activity. We trained rats on a continuous multiple-trial Morris water maze (MWM) task and then subjected them to a 24-hour probe trial retrieval test while they were under the influence of a subhypnotic dose of propofol. We investigated the involvement of GSK-3 in memory retrieval by assessing levels of serine-9- and tyrosine-216-phosphorylated GSK-3, abbreviated herein as p-GSK-3(Ser9) and p-GSK-3(Tyr216), respectively, following MWM retrieval testing, with or without pretest propofol administration, relative to those in untested rats. == Materials and Methods == == Animals == Adult male Sprague-Dawley rats (10 weeks of age) were purchased from the Center of Experimental Animals, Xuzhou Medical College, China, a specific-pathogen-free level laboratory authorized by the Jiangsu provincial government of China (production license for experimental animals, SCXK2010-0003). On their arrival, the rats were housed four per cage at a constant temperature of 24 1C, under a 12-hour light-dark cycle, with unlimited access to food and water for 1 week before behavioral training. All experiments were approved by the Animal Ethics Committee of.