Antidepressant Effects of (S)-Ketamine through a Reduction of Hyperpolarization-Activated Current I_h.

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 I_h of dorsal CA1 neurons in unstressed rats, whereas (S)-ketamine decreased both somatic and dendritic I_h in chronic unpredictable stress (CUS) rats. The reduction of I_h 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 n

SUBMITTER: Kim CS 

PROVIDER: S-EPMC7322259 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature