Dexamethasone and stressor-magnitude regulation of stress-induced transcription of HPA axis secretagogues in the rat

Regulation of the production of hypothalamic-pituitary-adrenal (HPA) axis secretagogues, corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP), may be differentially sensitive to the negative feedback effects of glucocorticoids. We chose to study this phenomenon by examining the ability of dexamethasone to influence CRH and AVP heteronuclear RNA (hnRNA) levels in an escapable/inescapable (ES/IS) foot-shock stress paradigm. On Day 1, adult male rats were subjected to either ES or IS foot-shock; on Day 2, saline or dexamethasone (100g/kg) was administered 2h prior to the stressor. We found that ES/IS foot-shock stimulated similar robust increases in plasma adrenocorticotrophic hormone (ACTH) and corticosterone concentrations, and medial parvocellular division of the paraventricular nucleus (mpPVN) AVP and CRH hnRNA and c-fos mRNA levels in saline-treated ES/IS rats. Dexamethasone pretreatment suppressed ACTH and corticosterone levels similarly in IS and ES animals. Dexamethasone pretreatment also suppressed mpPVN CRH and AVP hnRNA levels at 30min. However, by 120min, the mpPVN AVP hnRNA levels in dexamethasone-treated rats were similar to those measured in the saline group. We also found that rats that received the most shocks on Day 1 had greater HPA axis activation on Day 2. We conclude that the magnitude of the foot-shock stressor, determined by learned and immediate cues, is important in determining the magnitude of the HPA response.