Adolescent Stress Confers Resilience to Traumatic Stress Later in Life: Role of the Prefrontal Cortex

Abstract

Stress during adolescence is usually associated with psychopathology later in life. However, under certain circumstances, developmental stress can promote an adaptive phenotype, allowing individuals to cope better with adverse situations in adulthood, thereby contributing to resilience. The aim of the study was to understand how adolescent stress alters behavioral and physiological responses to traumatic stress in adulthood. Sprague Dawley rats were subjected to adolescent chronic variable stress (adol CVS) followed by single prolonged stress (SPS) in adulthood. One week after SPS, animals were tested for acquisition, extinction, extinction recall and reinstatement of auditory-cued fear conditioning, with neuronal recruitment during reinstatement assessed by Fos expression. Patch clamp electrophysiology was performed to examine physiological changes associated with resilience. We observed that adol CVS blocked SPS-induced impairment of extinction learning (males) and enhancement fear reinstatement (both sexes). SPS effects were associated with a reduction of infralimbic (IL) cortex neuronal recruitment after reinstatement in males and increased engagement of the central amygdala in females, both of which were also prevented by adol CVS. We explored the mechanism behind reduced IL recruitment in male rats by studying the intrinsic excitability of IL pyramidal neurons. SPS reduced excitability of IL neurons and prior adol CVS prevented this effect, indicating that adolescent stress can impart resilience to the effects of traumatic stress by modification of IL output in males. Overall, our study suggests that prior stress exposure can limit the impact of a subsequent severe stress exposure in adulthood, effects that are mediated by sex-specific modification of infralimbic and amygdala signaling.