期刊
INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
卷 13, 期 9, 页码 1255-1260出版社
OXFORD UNIV PRESS
DOI: 10.1017/S1461145710000544
关键词
AMPA receptors; antidepressants; NMDA receptors
资金
- VIGONI
- Italian Ministry of Health
- Deutsche Forschungsgemeinschaft [GA427/8-1, SFB636-B3]
Glutamate and its receptors are involved in the pathophysiology of mood disorders and have recently emerged as potential targets for the pharmacotherapy of depression. In rats, we investigated plasticity changes of the glutamatergic system evoked by electroconvulsive shock (ECS), which represents the most effective therapy for patients who are refractory to antidepressants. Chronic ECS produced a marked increase in the phosphorylation of the regulatory NMDA receptor subunit NR2B (Ser(1303)) and the AMPA receptor subunit GluR-A (Ser(831)) in the hippocampus, with no effects on the obligatory subunit NR1. No effects were found on total receptor subunit expression levels. We suggest that, at least in part, ECS exerts its clinical activity through the modulation of the glutamatergic synapses, via potentiation of AMPA currents mediated by GluR-A (Ser(831)) phosphorylation, and a reduction of NMDA receptor activity through the phosphorylation of NR2B (Ser(1303)), presumably uncoupling NR2B from its signalling partner CaMKII. These effects functionally resemble the recently described antidepressant effects of ketamine.
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