Lasting Impact of Chronic Adolescent Stress and Glucocorticoid Receptor Selective Modulation in Male and Female Rats.

Autor: Cotella EM; Dept. Pharmacology & Systems Physiology, University of Cincinnati, Cincinnati, OH, United States., Morano RL; Dept. Pharmacology & Systems Physiology, University of Cincinnati, Cincinnati, OH, United States., Wulsin AC; Dept. Pharmacology & Systems Physiology, University of Cincinnati, Cincinnati, OH, United States., Martelle SM; Dept. Pharmacology & Systems Physiology, University of Cincinnati, Cincinnati, OH, United States., Lemen P; Dept. Pharmacology & Systems Physiology, University of Cincinnati, Cincinnati, OH, United States., Fitzgerald M; Dept. Pharmacology & Systems Physiology, University of Cincinnati, Cincinnati, OH, United States., Packard BA; Dept. Pharmacology & Systems Physiology, University of Cincinnati, Cincinnati, OH, United States., Moloney RD; Dept. Pharmacology & Systems Physiology, University of Cincinnati, Cincinnati, OH, United States., Herman JP; Dept. Pharmacology & Systems Physiology, University of Cincinnati, Cincinnati, OH, United States. Electronic address: hermanjs@ucmail.uc.edu.
Jazyk: angličtina
Zdroj: Psychoneuroendocrinology [Psychoneuroendocrinology] 2020 Feb; Vol. 112, pp. 104490. Date of Electronic Publication: 2019 Oct 27.
DOI: 10.1016/j.psyneuen.2019.104490
Abstrakt: Adolescent animals are vulnerable to the effects of stress on brain development. We hypothesized that long-term effects of adolescent chronic stress are mediated by glucocorticoid receptor (GR) signaling. We used a specific GR modulator (CORT108297) to pharmacologically disrupt GR signaling in adolescent rats during exposure to chronic variable stress (CVS). Male and female rats received 30 mg/kg of drug during a 2-week CVS protocol starting at PND46. Emotional reactivity (open field) and coping behaviors (forced swim test (FST)) were then tested in adulthood, 5 weeks after the end of the CVS protocol. Blood samples were collected two days before FST and serial samples after the onset of the swim test to determine baseline and stress response levels of HPA hormones respectively. Our results support differential behavioral, physiological and stress circuit reactivity to adolescent chronic stress exposure in males and females, with variable involvement of GR signaling. In response to adolescent stress, males had heightened reactivity to novelty and exhibited marked reduction in neuronal excitation following swim stress in adulthood, whereas females developed a passive coping strategy in the FST and enhanced HPA axis stress reactivity. Only the latter effect was attenuated by treatment with the GR modulator C108297. In summary, our data suggest that adolescent stress differentially affects emotional behavior and circuit development in males and females, and that GR manipulation during stress can reverse at least some of these effects.
(Copyright © 2019 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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