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- W3034150624 endingPage "101239" @default.
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- W3034150624 abstract "Compelling evidence suggests that a single sub-anesthetic dose of (R,S)-ketamine exerts rapid and robust antidepressant effects. However, the cellular mechanisms underlying the antidepressant effects of (R,S)-ketamine remain unclear. Here, we show that (S)-ketamine reduced dendritic but not somatic hyperpolarization-activated current Ih of dorsal CA1 neurons in unstressed rats, whereas (S)-ketamine decreased both somatic and dendritic Ih in chronic unpredictable stress (CUS) rats. The reduction of Ih by (S)-ketamine was independent of NMDA receptors, barium-sensitive conductances, and cAMP-dependent signaling pathways in both unstressed and CUS groups. (S)-ketamine pretreatment before the onset of depression prevented CUS-induced behavioral phenotypes and neuropathological changes of dorsal CA1 neurons. Finally, in vivo infusion of thapsigargin-induced anxiogenic- and anhedonic-like behaviors and upregulation of functional Ih, but these were reversed by (S)-ketamine. Our results suggest that (S)-ketamine reduces or prevents Ih from being increased following CUS, which contributes to the rapid antidepressant effects and resiliency to CUS." @default.
- W3034150624 created "2020-06-12" @default.
- W3034150624 creator A5003399059 @default.
- W3034150624 creator A5010467709 @default.
- W3034150624 date "2020-06-01" @default.
- W3034150624 modified "2023-10-13" @default.
- W3034150624 title "Antidepressant Effects of (S)-Ketamine through a Reduction of Hyperpolarization-Activated Current I" @default.
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- W3034150624 doi "https://doi.org/10.1016/j.isci.2020.101239" @default.
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