The cellular mechanisms underlying
amnesia produced by the
analgesic ketamine are not clear. The current study examined the effects of
ketamine on memory consolidation in rats trained in a Morris water maze task, and further tested whether the
glycogen synthase kinase (GSK)3β/β-
catenin signaling pathway was involved in mediating the effects of posttraining
ketamine on retention. Adult male Sprague-Dawley rats were injected with
ketamine (0, 25, 50, or 100mg/kg) immediately after an eight-trial water maze training session. A probe trial was carried out 24 h later to examine the effects of
ketamine on memory. Rats hippocampi were subjected to western blot assays to measure levels of native versus phosphorylated (p) GSK3β and β-
catenin protein. Memory performance was significantly impaired in rats injected with
ketamine (100 mg/kg) after training. Western blots showed that p-GSK-3β(Ser9) levels were reduced and p-β-
catenin(Ser33/37/Thr41) levels were elevated in
ketamine treated rats during consolidation. These posttraining changes in hippocampal p-GSK-3β and p-β-
catenin were blocked by injection of 100mg/kg
ketamine immediately after training, indicating that the 100mg/kg dose of
ketamine altered activation of GSK3β/β-
catenin signaling pathway in the hippocampus. Acute injection of the GSK3β specific inhibitor
SB216763 (1 ng/0.5 μl/side) into area CA1 of the hippocampus after water maze training prevented
ketamine-induced impairment of memory and blocked
ketamine-induced effects on the GSK3β/β-
catenin signaling pathway in the hippocampus. Our results suggest that an
anesthetic dose of
ketamine injected immediately after Morris water maze training impaired memory consolidation and support the hypothesis that GSK3β/β-
catenin signaling may play a role in
ketamine-induced
retrograde amnesia.