Previous studies have indicated that stress-activated glucocorticoid hormones induce temporary memory retrieval impairment. The present study examined whether adrenal steroid receptors in the hippocampus mediate such glucocorticoid effects on spatial memory retrieval. The specific glucocorticoid receptor (GR) agonist 11␤, 17␤-dihydroxy-6,21-dimethyl-17␣-pregna-4,6-trien-20yn-3-one (RU 28362; 5 or 15 ng) infused into the hippocampus of male Sprague-Dawley rats 60 min before water-maze retention testing, 24 h after training, dose-dependently impaired probe-trial retention performance, as assessed both by time spent in the training quadrant and initial latency to cross the platform location. The GR agonist did not affect circulating corticosterone levels immediately after the probe trial, indicating that RU 28362 infusions did not influence retention by altering glucocorticoid feedback mechanisms. As infusions of the GR agonist into the hippocampus 60 min before training did not influence water-maze acquisition or immediate recall, the findings indicated that the GR agonist-induced retention impairment was induced selectively by an influence on information retrieval. In contrast, pretest infusions of the GR agonist administered into the basolateral complex of the amygdala (BLA; 2 or 6 ng) did not alter retention performance in the water maze. However, N-methyl-D-aspartate-induced lesions of the BLA, made 1 week before training, blocked the memory retrieval impairment induced by intrahippocampal infusions of RU 28362 given 60 min before the retention test. These findings indicate that the effects of glucocorticoids on retrieval of long-term spatial memory depend on the hippocampus and, additionally, that neuronal input from the BLA is critical in enabling hippocampal glucocorticoid effects on memory retrieval.corticosterone ͉ glucocorticoid receptor ͉ stress hormone ͉ water maze I t is well established that adrenocortical hormones (corticosterone in rats, cortisol in humans) influence many aspects of cognitive performance. Studies of acute glucocorticoid effects on distinct memory phases have revealed that a single administration of glucocorticoids enhances the formation of new memories and, additionally, impairs the recall of previously learned information (1-3). Considerable evidence supports a role for the hippocampus in mediating glucocorticoid enhancement of memory consolidation. For example, either systemic or intracerebroventricular administration of glucocorticoids or specific antagonists inf luences consolidation of hippocampusdependent spatial or contextual information (4-9). Furthermore, posttraining intrahippocampal infusions of corticosterone or synthetic glucocorticoid receptor (GR) agonists enhance memory consolidation on a variety of tasks, whereas infusions of a GR antagonist or GR antisense impair memory consolidation (10-16). The basolateral complex of the amygdala (BLA; consisting of the lateral, basal, and accessory basal nuclei) is also a critical component of the neural circuitry mediating glu...