THE EFFECT OF NMDA RECEPTOR ANTAGONIST TREATMENT ON ERK1/2-S6K-S6 SIGNAL PAHTWAY AND PROTEIN SYNTHESIS IN DEVELOPING RAT BRAIN

Abstract

Treatment of MK-801, a selective NMDA receptor antagonist, on neonatal rat induces long-term neurochemical and behavioral changes, which is suggested as neurodevelopmental rat model of schizophrenia. Proper regulation of protein synthesis is required for neurodevelopment process. Here, effects of MK-801 treatment at PN7 on p70S6K and mTOR signal pathways related to protein translation and protein synthesis rate were examined in frontal cortex of developing rat brain. Single injection of MK-801, 0.5 and 1.0 mg/kg, induced significant decrease in the of phosphorylation of p70S6K, S6, and eIF4B until 8 h. Two injections of MK-801 induced more prominent changes. These changes were accompanied with changes in ERK1/2-p90RSK pathway along with Egr-1 expression, but not with AKT-mTOR pathway. Moreover, two injections of MK-801, 1.0 mg/kg, induced significant decrease in protein synthesis rate at 8 h, which was measured by [3H] leucin incorporation. In addition, MK-801 treatments at PN7 induced increase in locomotor activity and deficits in prepulse inhibition at PN56. Taken together, neonatal treatment of MK-801 induces dysregulation in ERK1/2-p70S6K-S6 pathway and protein synthesis rate in frontal cortex of developing rat brain with long-term behavioral changes.