TY - JOUR
T1 - Enhancing AMPA to NMDA throughput as a convergent mechanism for antidepressant action
AU - Du, Jing
AU - Machado-Vieira, Rodrigo
AU - Maeng, Sungho
AU - Martinowich, Keri
AU - Manji, Husseini K.
AU - Zarate, Carlos A.
N1 - Funding Information:
This study was supported by the Intramural Research Program at the National Institute of Mental Health, National Institutes of Health, and Department of Health & Human Services, The Stanly Medical Research Institute and NARSAD.
PY - 2006/6
Y1 - 2006/6
N2 - In this article, we first review current knowledge of the AMPA and NMDA glutamate receptors, their physiological properties and functions and their regulation by signaling cascades. We then discuss our hypothesis that the therapeutic effects of monoaminergic antidepressants and ketamine, an NMDA receptor antagonist, may be mediated by increased AMPA to NMDA throughput in critical neuronal circuits. We hypothesize that ketamine mediates this throughput directly, thus resulting in rapid antidepressant effects whereas monoaminergic antidepressants work indirectly and gradually; this may explain, in part, the delayed onset of several weeks to months that is observed with traditional antidepressants.
AB - In this article, we first review current knowledge of the AMPA and NMDA glutamate receptors, their physiological properties and functions and their regulation by signaling cascades. We then discuss our hypothesis that the therapeutic effects of monoaminergic antidepressants and ketamine, an NMDA receptor antagonist, may be mediated by increased AMPA to NMDA throughput in critical neuronal circuits. We hypothesize that ketamine mediates this throughput directly, thus resulting in rapid antidepressant effects whereas monoaminergic antidepressants work indirectly and gradually; this may explain, in part, the delayed onset of several weeks to months that is observed with traditional antidepressants.
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U2 - 10.1016/j.ddstr.2006.11.012
DO - 10.1016/j.ddstr.2006.11.012
M3 - Review article
C2 - 25411578
AN - SCOPUS:33846158094
SN - 1740-6773
VL - 3
SP - 519
EP - 526
JO - Drug Discovery Today: Therapeutic Strategies
JF - Drug Discovery Today: Therapeutic Strategies
IS - 4
ER -