The resilience of adolescent male rats to acute stress-induced delayed anxiety is age-related and glucocorticoid release-dependent

Neuropharmacology. 2023 Mar 15:226:109385. doi: 10.1016/j.neuropharm.2022.109385. Epub 2023 Jan 2.

Abstract

Studies investigated how stressful experiences modulate physiological and behavioral responses and the consequences of stress-induced corticosterone release in anxiety-like behavior. Adolescence is crucial to brain maturation, and several neurobiological changes in this period lead individuals to increased susceptibility or resilience to aversive situations. Despite the effects of stress in adults, information about adolescents' responses to acute stress is lacking. We aimed to understand how adolescence affects acute stress responses. Male adolescent rats (30 days old) were 2 h restrained, and anxiety-like behaviors were measured immediately or 10 days after stress in the elevated plus-maze (EPM) and the light-dark box (LDB) tests. To verify the importance of CORT modulation in stress-induced anxiety, another group of rats was treated, 30 min before restraint, with metyrapone to blunt the stress-induced CORT peak and tested immediately after stress. To show that stress effects on behavior were age-dependent, another set of rats was tested in two different periods - early adolescence (30 days old) and mid-adolescence (40 days old) and were treated or not with metyrapone before the stress session and tested immediately or ten days later in the LDB test. Only early adolescent male rats were resilient to delayed anxiety-like behavior in EPM and LDB tests. Metyrapone treatment increased the rats' exploration immediately and ten days after stress. These data suggest a specific age at which adolescent rats are resilient to the delayed effects of acute restraint stress and that the metyrapone treatment has long-term behavioral consequences.

Keywords: Elevated plus maze; HPA-Axis; Light-dark box; Metyrapone; Restraint stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anxiety / chemically induced
  • Anxiety Disorders
  • Behavior, Animal
  • Corticosterone / pharmacology
  • Glucocorticoids* / pharmacology
  • Male
  • Metyrapone* / pharmacology
  • Rats
  • Stress, Psychological / complications

Substances

  • Glucocorticoids
  • Metyrapone
  • Corticosterone