The Raab-Graham lab recently published a research article in the journal Molecular Psychiatry entitled “Rapid Antidepressant Stimulates 14-3-3η Decoupling of GABABR from GIRK/Kir3″. For over 20 years it has been known that N-methyl-D-aspartate receptor (NMDAR) antagonists are effective as rapid antidepressants, however the underlying molecular mechanism of how NMDAR antagonists caused neuroadaptive changes in the brain leading to their antidepressive efficacy has been unknown. This work reveals that NMDAR antagonism reduces the major inhibitory receptor (GABABR) signaling to inwardly rectifying potassium (Kir3) channels. which in turn is mediated by increased expression of the decoupling adapter protein 14-3-3η.
Workman ER, Haddick PCG, Bush KM, Niere F, Dilly GA, Zemelman B V, and Raab-Graham KF. 2015. Rapid Antidepressant Stimulates 14-3-3η Decoupling of GABABR from GIRK/Kir3. Molecular Psychiatry. In press.