Ketamine Administration Reverses Corticosterone-Induced Alterations in Excitatory and Inhibitory Transmission in the Rat Dorsal Raphe Nucleus

Abstract

Ketamine, a N-methyl-D-aspartate (NMDA) receptor antagonist, exerts rapid antidepressant effects in human patients and ameliorates depressive-like behavioral effects of chronic stress in animal models. Chronic stress and elevated corticosterone levels have been shown to modify serotonin (5-HT) neurotransmission, and ketamine’s antidepressant-like activity involves a 5-HT-dependent mechanism. However, it is not known if and how ketamine affects the electrophysiological characteristics of neurons and synaptic transmission within the dorsal raphe nucleus (DRN), the main source of 5-HT forebrain projections. Our study was aimed at investigating the effects of a single ketamine administration on excitatory and inhibitory transmission in the DRN of rats which had previously been administered corticosterone twice daily for 7 days. Spontaneous excitatory and inhibitory postsynaptic currents (sEPSCs and sIPSCs) were then recorded from DRN projection cells in ex vivo slice preparations obtained 24 h after ketamine injection. Repeated corticosterone administration increased sEPSC frequency and decreased sIPSC frequency in DRN projection cells. There were no changes either in the amplitude of postsynaptic currents or in the excitability of these cells. In slices prepared from rats with ketamine administered after the end of corticosterone treatment, the frequencies of sEPSCs and sIPSCs were similar to those in control preparations. These data indicate that a single administration of ketamine reversed the effects of corticosterone on excitatory and inhibitory transmission in the DRN.

Prenatal stress‐related alterations in synaptic transmission and 5‐HT7 receptor‐mediated effects in the rat dorsal raphe nucleus are ameliorated by the 5‐HT7 receptor antagonist SB 269970

“…We have previously observed a superficially similar reduction in the frequency of sIPSCs which occurred in rat DRN projection neurons after repeated corticosterone administration (Sowa, Kusek, Bobula, Hess, & Tokarski, 2019; Sowa et al., 2018). Moreover, we have found that long‐lasting elevation in plasma corticosterone levels increases sEPSC frequency in DRN projection cells (Sowa et al., 2019), which resembles our current observations.…”

“…We have previously observed a superficially similar reduction in the frequency of sIPSCs which occurred in rat DRN projection neurons after repeated corticosterone administration (Sowa, Kusek, Bobula, Hess, & Tokarski, 2019; Sowa et al., 2018). Moreover, we have found that long‐lasting elevation in plasma corticosterone levels increases sEPSC frequency in DRN projection cells (Sowa et al., 2019), which resembles our current observations. Prenatal stress imposed by a procedure identical to the one used in the present study and performed on the same rat strain (Sprague‐Dawley) has earlier been shown to induce a hyperactivity of the hypothalamic–pituitary–adrenal (HPA) axis in response to acute stressors and to elevate basal plasma corticosterone levels at least during part of the day (Szymańska et al., 2009).…”

Differential effects of repeated fluoxetine and ketamine administration on behavioral and pharmacological stressor-induced depression of digging behavior in mice.

“…Interestingly, ketamine failed to reverse swim stress-induced decrease of digging; however, this could be due to a compounding effect as a single injection of ketamine has been shown to increase corticosterone in rats following chronic corticosterone administration (Wegman-Points et al, 2020). However, there are plenty of studies demonstrating ketamine’s ability to reverse corticosterone-induced depression of behavior and cellular signaling (Fraga et al, 2021; Sowa et al, 2019; Wang et al, 2019). The lack of ketamine effect in following swim stress could be due to several variables including, but not limited to, dose tested, pretreatment time on test days, and/or dosing regimen.…”

Erratum to “Ketamine Administration Reverses Corticosterone-Induced Alterations in Excitatory and Inhibitory Transmission in the Rat Dorsal Raphe Nucleus”

“…In the article titled “Ketamine administration reverses corticosterone-induced alterations in excitatory and inhibitory transmission in the rat dorsal raphe nucleus” [ 1 ], there was an error in Figures 2 and 3 . Figures 2 and 3 images were swapped.…”