OXYTOCIN REDUCES THE ACTIVITY OF N-METHYL-D-ASPARTATE RECEPTORS IN CULTURED NEURONS

N-Methyl-D-Aspartate(NMDA)-sensitive glutamate receptors, are critically involved in the induction of the learning process. Activation of NMDA receptors by glutamate lead to massive influx of extracellular Ca2+, with ensuing activation of a variety of Ca2+-dependent enzymes, including protein kinase C. This triggers a cascade of intracellular reactions which is essential for memory formation. In culture neurons, high concentrations of oxytocin (> l muM) attenuate the stimulation of Ca-45(2+) influx promoted by glutamate through the activation NMDA receptors. In addition, the hormone reduces glutamate-stimulated [H-3]4-beta-phorbol 12,13-dibutyrate (PdBu) binding in intact cells, a parameter that reflects the translocation of protein kinase C from the cytosol to the cell membrane. Taken collectively, these results indicate that oxytocin reduces the activity of NMDA receptors, thus impairing one of the major substrates for the induction of learning and memory.