RT Journal Article SR Electronic T1 The Rac1 Inhibitor NSC23766 Suppresses CREB Signaling by Targeting NMDA Receptor Function JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 14006 OP 14012 DO 10.1523/JNEUROSCI.1659-14.2014 VO 34 IS 42 A1 Hou, Hailong A1 Chávez, Andrés E. A1 Wang, Chih-Chieh A1 Yang, Hongtian A1 Gu, Hua A1 Siddoway, Benjamin A. A1 Hall, Benjamin J. A1 Castillo, Pablo E. A1 Xia, Houhui YR 2014 UL http://www.jneurosci.org/content/34/42/14006.abstract AB NMDA receptor signaling plays a complex role in CREB activation and CREB-mediated gene transcription, depending on the subcellular location of NMDA receptors, as well as how strongly they are activated. However, it is not known whether Rac1, the prototype of Rac GTPase, plays a role in neuronal CREB activation induced by NMDA receptor signaling. Here, we report that NSC23766, a widely used specific Rac1 inhibitor, inhibits basal CREB phosphorylation at S133 (pCREB) and antagonizes changes in pCREB levels induced by NMDA bath application in rat cortical neurons. Unexpectedly, we found that NSC23766 affects the levels of neuronal pCREB in a Rac1-independent manner. Instead, our results indicate that NSC23766 can directly regulate NMDA receptors as indicated by their strong effects on both exogenous and synaptically evoked NMDA receptor-mediated currents in mouse and rat neurons, respectively. Our findings strongly suggest that Rac1 does not affect pCREB signaling in cortical neurons and reveal that NSC23766 could be a novel NMDA receptor antagonist.