Homeostatic interaction of N-methyl-D-aspartate receptor (NMDAR) and γ-aminobutyric acid receptor B (GABABR)

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2016-01-13

Authors

Workman, Emily Rush

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Abstract

N-methyl-D-aspartate receptor (NMDAR) antagonists have gained much attention of late for their ability to remediate major depressive disorder. The body of evidence surrounding their mechanism of action suggests that they activate cellular homeostatic mechanisms. This thesis examines the convergence of rapid antidepressant and homeostatic mechanisms. It provides evidence of the homeostatic interaction between NMDAR and γ-aminobutyric acid receptor B (GABABR), a metabotropic inhibitory receptor, by demonstrating that GABABR function shifts from opening inwardly rectifying potassium channels to increasing resting dendritic calcium signal upon application of NMDAR antagonists. This fundamental shift in function plays an important role in the activation of protein synthesis dependent homeostatic mechanisms that occur in response to NMDAR antagonists. We hypothesize that the GABABR shift in function is a unifying pathway between rapid antidepressant and local homeostatic mechanisms.

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