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Role of GPCRs and G‐α s in the antidepressant action of ketamine
Author(s) -
Wray Nathan,
Schappi Jeffrey,
Rasenick Mark M
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.664.10
Subject(s) - lipid raft , adenylyl cyclase , creb , antidepressant , ketamine , intracellular , chemistry , pharmacology , raft , cyclic adenosine monophosphate , endocrinology , medicine , microbiology and biotechnology , receptor , hippocampus , biology , neuroscience , transcription factor , biochemistry , organic chemistry , copolymer , gene , polymer
Ketamine produces rapid and robust antidepressant effects in depressed patients within hours of administration, often when traditional antidepressant compounds have failed to alleviate symptoms even after 2 months of treatment. We hypothesized that ketamine would translocate Ga s from lipid rafts to non‐raft microdomains, similarly to other antidepressants but with a distinct, abbreviated treatment duration. C6 glioma and C6 cells stably transfected with G‐α s ‐GFP were treated with 10uM ketamine for 15 minutes, which translocated Ga s from lipid raft domains to non‐raft domains. Other NMDA antagonist did not translocate Ga s from lipid raft to non‐raft domains. The ketamine induced Ga s plasma membrane redistribution allows increased functional coupling of Ga s and adenylyl cyclase to increase intracellular cyclic adenosine monophosphate (cAMP). Furthermore, increased intracellular cAMP increased phosphorylation of cAMP response element‐binding protein (CREB), which, in turn, increased BDNF expression. These results reveal a novel antidepressant mechanism mediated by acute ketamine treatment in glial cells that may contribute to ketamine's powerful antidepressant effect.