Glucocorticoid receptor inhibition prevents lasting endocrine but not behavioral effects of adolescent stress

COTELLA, EVELIN M.; MORANO, RACHEL L.; WULSIN, AYNARA C.; MARTELLE, SUSAN E.; HERMAN, JAMES P.

Zurich

Congreso; International Society of Psychoneuroendocrinology; 2017

International Society of Psychoneuroendocrinology

We hypothesized that adolescent chronic stress causes life-long impairment in behavioral and physiological adaptations tostressful experiences and this is mediated by glucocorticoid recep-tor (GR) signalling. Starting PND46, CORT108297 (30 mg/kg) GRblocker was injected during a 2-week protocol of chronic vari-able stress (CVS). Groups: Control-Vehicle; Control-CORT108297;CVS-Vehicle and CVS-CORT108297. At PND90 they were tested foropen field activity; on PND94 tail blood was taken for baseline cor-ticosterone and ACTH; at PND98 they were tested in the forcedswim test (FST, 10 min, 25±2◦). Blood samples were collected 15,30, 60 and 120 min after the onset of swim to determine HPAresponse to stress. In females, CVS increased corticosterone, ACTHand adrenal sensitivity at baseline and elevated corticosterone lev-els and adrenal sensitivity in response to stress. The changes incorticosterone and adrenal sensitivity were completely preventedby CORT108297, suggesting an active role of GR programming HPAactivity in adaptation to adolescent CVS. There were no endocrineeffects of adolescent CVS on males. Regarding behavior, FST loco-motor activity of females stressed during adolescence was reducedand was not affected by inhibition of GR. Males had increasedanxiety-like behavior in the open field that was not affected byCORT108297. In summary, we observed that female HPA activ-ity is elevated by CVS during adolescence by a GR-dependentmechanism. Conversely, behavioral effects observed in females(depression-like behavior) and males (anxiety-like behavior) areindependent of chronic stress-induced GR activation. Mapping ofc-Fos activation after forced swim test is currently underway sup-ported by MH101729.