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. 2020 Nov 30;11:590221. doi: 10.3389/fphar.2020.590221

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Copyright © 2020 Wegman‐Points, Pope, Zobel-Mask, Winter, Wauson, Duric and Yuan

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Schematic representation of the timeline for oral corticosterone exposure, drug administration, and tissue collection. (A) The rats were provided with water containing 50 μg/ml of corticosterone for 2 weeks, after which the dosage was tapered off with 3 days to 25 μg/ml followed by three more days at 12.5 μg/ml. The rats were returned to regular drinking water for 3–7 days to wash out exogenous corticosterone before injection and sacrifice. The rats with access to drinking water throughout the 4-week period served as naïve controls. Measurement of corticosterone levels in serum and brain tissue in male and female rats 1-h post injection. Ci-stress male and female rats received injection of saline (male n = 11; female n = 6), ketamine (10 mg/kg) (male n = 11; female n = 6) or HNK (10 mg/kg) (male n = 6; female n = 6). Naïve rats received only saline (male n = 12; female n = 6). (B) Circulating corticosterone levels in male rats. (C) Cortical brain levels of corticosterone in male rats. (D) Circulating corticosterone levels in female rats. (E) Cortical brain levels of corticosterone in female rats. Measurement of serum corticosterone levels 1-h post injection of naïve rats (F). Timeline of naïve male treatment and tissue collection. (G) Ketamine injection caused an increase in circulating corticosterone versus saline injection in naïve rats (saline n = 5, ketamine n = 5). [(B–D) ***p < 0.001, ****p < 0.0001, two-way ANOVA with Tukey post-test, (G) ***p < 0.001, student t-test).