Increased phosphorylation of Ser473-Akt, Ser9-GSK-3β and Ser133-CREB in the rat frontal cortex after MK-801 intraperitoneal injection

GSK-3 beta is regarded as playing an important part in the pathogenesis of schizophrenia and the action of psychotomimetic agents. We observed phosphorylation of molecules associated with the GSK-3 beta signalling pathway in the rat brain after MK-801 injection, which induces a schizophrenia-like state in humans. Ser9-GSK-3 beta phosphorylation was increased after injection of 1 mg/kg MK-801 in the rat frontal cortex but not in the hippocampus or cerebellum. This increase peaked at 30 min and was maintained until 90 min after injection. The phosphorylation showed a close-dependent increase up to I mg/kg MK-801, followed by a decrease at higher dosage. Furthermore, phosphorlation of Ser473-Akt and Ser133-CREB showed similar temporal, dose-dependent and regionally specific patterns with those of Ser9-GSK-3 beta. However, phosphorylation of Dvl and Ser33-beta-catenin was not affected bv MK-801. These results suggest that GSK-3 beta phosphorylation by MK-801 may be associated with the Akt-GSK-3 beta pathway rather than with the Wnt-Dvl-GSK3 beta pathway.