Vol.:(0123456789) 1 3 Pharmacological Reports https://doi.org/10.1007/s43440-022-00366-z ARTICLE Exposure to chronic stressor upsurges the excitability of serotoninergic neurons and diminishes concentrations of circulating corticosteroids in rats two weeks thereafter Eliyahu Dremencov 1,2  · Daniil Grinchii 1  · Katarina Hrivikova 2  · Maxim Lapshin 3  · Maria Komelkova 3,4,5  · Jan Graban 2  · Agnesa Puhova 2  · Olga Tseilikman 3,4  · Vadim Tseilikman 3  · Daniela Jezova 2 Received: 24 November 2021 / Revised: 24 March 2022 / Accepted: 30 March 2022 © The Author(s) under exclusive licence to Maj Institute of Pharmacology Polish Academy of Sciences 2022 Abstract Background Exposure to predator scent (PS) has been used as a model of stress associated with danger to life and body integrity. Under stress conditions, the brain serotoninergic (5-HT) system plays an important role. Methods We tested the hypothesis that repeated PS exposure alters the excitability of 5-HT neurons of the dorsal raphe nucleus. To study the mechanisms involved, we approached serum and adrenal corticosterone and aldosterone concentrations, as well as brain-derived neurotrophic factor (BDNF) expression. Adult male Sprague–Dawley rats were exposed to PS for 10 min daily for 10 consecutive days. Two weeks after the last exposure, electrophysiological and biochemical assessments were performed. Results Measurements by in vivo electrophysiology showed increased fring activity of 5-HT neurons in rats exposed to PS. Exposure to PS resulted in reduced serum corticosterone and aldosterone concentrations. Concentrations of both corticos- teroids in the adrenal glands and the relative weight of the adrenals were unafected. The gene expression of hippocampal BDNF of rats exposed to PS remained unaltered. PS exposure failed to induce changes in the gene expression of selected adrenal steroidogenic factors. Conclusion Reduced corticosteroid concentrations in the blood appear to be the result of increased metabolism and/or tis- sue uptake rather than altered steroidogenesis. The decrease in circulating corticosterone in rats who experienced repeated PS may represent part of the mechanisms leading to increased excitability of 5-HT neurons. The increase in 5-HT neuronal activity might be an important compensatory mechanism designated to diminish the harmful efects of the repeated PS exposure on the brain. Keywords Predator scent · Aldosterone · Brain-derived neurotrophic factor (BDNF) · Corticosterone · Adrenal gland · Dorsal raphe nucleus (DRN) · Electrophysiology · Serotonin (5-HT) Abbreviations 5-HT Serotonin BDNF Brain-derived neurotrophic factor DRN Dorsal raphe nucleus GAD Generalized anxiety disorder GR Glucocorticoid receptors PD Panic disorder PPIA Peptidyl prolyl isomerase A PCR Polymerase chain reaction PTSD Post-traumatic stress disorder PS Predator scent RPS29 Ribosomal protein S29 GABA γ-aminobutyric acid CYP11B1 Steroid 11β-hydroxylase StAR Steroidogenic acute regulatory protein * Eliyahu Dremencov Eliyahu.Dremencov@savba.sk 1 Institute of Molecular Physiology and Genetics, Center of Biosciences, Slovak Academy of Sciences, Bratislava, Slovak Republic 2 Institute of Experimental Endocrinology, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovak Republic 3 School of Medical Biology, South Ural State University, Chelyabinsk, Russian Federation 4 Faculty of Fundamental Medicine, Chelyabinsk State University, Chelyabinsk, Russian Federation 5 Institute of Immunology and Physiology, Ural Division of the Russian Academy of Sciences, Ekaterinburg, Russian Federation