SELECTIVE POTENTIATION OF DNA-BINDING ACTIVITIES OF BOTH ACTIVATOR PROTEIN-1 AND CYCLIC-AMP RESPONSE ELEMENT-BINDING PROTEIN THROUGH IN-VIVO ACTIVATION OF N-METHYL-D-ASPARTATE RECEPTOR COMPLEX IN MOUSE-BRAIN

DNA binding activities of several transcription factors were evaluated in nuclear extracts from brains of mice that were injected intracereb roventricularly with N-methyl-D-aspartic acid (NMDA) using gel-shift a ssays. An injection of saline transiently increased binding of both pr obes for activator protein 1 (AP1) and cyclic AMP response element bin ding protein (CREB) 30 min after the injection, and NMDA was effective in inducing a more potent increment of binding of both probes 1-5 h a fter the injection than did saline. However, no significant alteration s were found in binding of probes for other transcription factors test ed up to 4 h following the injection of NMDA. The potentiation by NMDA was prevented in a dose-dependent manner by administration of the non competitive NMDA antagonist ,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,1 0-imine, the NMDA antagonist D,L-(E)-2-amino-4-propyl-5-phosphono-3-pe ntenoic acid, and the glycine antagonist 5,7-dichlorokynurenic acid, w hereas administration of the proposed polyamine antagonist ifenprodil was rather ineffective in protecting against the potentiation by NMDA. These results support the proposal that an intracerebroventricular in jection of NMDA may selectively potentiate DNA binding activities of b oth API and CREB through activation of the NMDA receptor complex in mo use brain.