Exposure to chronic stressor upsurges the excitability of serotoninergic neurons and diminishes concentrations of circulating corticosteroids in rats two weeks thereafter

Pharmacol Rep. 2022 Jun;74(3):451-460. doi: 10.1007/s43440-022-00366-z. Epub 2022 Apr 15.

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 firing activity of 5-HT neurons in rats exposed to PS. Exposure to PS resulted in reduced serum corticosterone and aldosterone concentrations. Concentrations of both corticosteroids in the adrenal glands and the relative weight of the adrenals were unaffected. 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 tissue 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 effects of the repeated PS exposure on the brain.

Keywords: Adrenal gland; Aldosterone; Brain-derived neurotrophic factor (BDNF); Corticosterone; Dorsal raphe nucleus (DRN); Electrophysiology; Predator scent; Serotonin (5-HT).

MeSH terms

  • Aldosterone / metabolism
  • Aldosterone / pharmacology
  • Animals
  • Brain-Derived Neurotrophic Factor / metabolism
  • Corticosterone*
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Serotonergic Neurons*
  • Serotonin / metabolism

Substances

  • Brain-Derived Neurotrophic Factor
  • Serotonin
  • Aldosterone
  • Corticosterone