Glucocorticoids (GCs) act via intracellular receptors which translocate into the nucleus to regulate target genes. There are two types of GC receptors, the high affinity mineralocorticoid receptor (MR) and the low affinity glucocorticoid receptor (GR). The secretion of GCs occurs in distinct pulses depending on numerous physiological factors (Atkinson et al. 2006); however, the functional significance of this pulsatility is unknown. Here, we present two models of corticosterone (cort) presentation in the rat: IP injection to mimic the prolonged cort release of a stress response and IV injection to mimic basal pulsatility. This study aims to determine how different patterns of cort presentation affect GR and MR activity in the hippocampus (HC), an important site for stress-related memory and learning. Male Sprague-Dawley rats (n=6/group) were anaesthetised with IM injection of Hypnorm (fentanyl citrate 0.252 mg/kg and fluanisone 8 mg/kg) after IP injection of Diazepam (4 mg/kg) then subjected to bilateral adrenalectomy and jugular cannulation (IV). After recovery for 5 days, each was given either 1 bolus IP injection (750 μg cort) or 2 bolus IV injections (100 μg cort) at times 0 and 120 min. Animals were killed at times 0, 10, 15, 30, 60 and 120 min. The HC was rapidly dissected and frozen. Nuclear extracts were prepared and analysed by Western blot with GR or MR antibodies to determine nuclear GR and MR levels. IP injection caused prolonged high plasma cort levels (466±164 ng/ml at 30 min, 206±31 ng/ml at 60 min) decreasing by 120 min (38±13 ng/ml). Nuclear translocation of both GR and MR in the HC was prolonged (21±4-fold GR, 23±5-fold MR at 30 min, and 14±4-fold GR, 31±5-fold MR at 60 min). IV injection caused a rapid pulse of GC (883±157 ng/ml) at 1 min. This was rapidly cleared as the half life of cort in blood is 10 min. Nuclear translocation of both GR and MR was observed in the HC at 10 min (19±6-fold GR, 14±3-fold MR) reaching a maximum at 15 min (22±9-fold GR, 19±4-fold MR). The retention time of GR in the nucleus was much shorter in duration than that observed after the IP injection. The depletion of nuclear GR after each pulse was evident by 30 min (9±2-fold) returning to near basal levels by 60 min. MR displayed a much slower nuclear depletion with high nuclear levels of MR throughout the time course decreasing only at 120 min after each pulse. Cort IP injection provides a model of a stress-like prolonged presence of GR and MR in HC nuclei as described by Kitchener et al. (2004). IV injection provides a temporal model of basal pulsatility with rapid turnover of GR but not MR in HC nuclei. Our findings have significant implications for GR as a sensitive mediator of adrenal GC pulses transmitted to the HC. The highly fluctuating nature of nuclear GR levels (but not MR levels) may be functionally important in allowing dynamic interactions with physiological responses e.g. stressors.