Glucocorticoid involvement in memory formation in a rat model for traumatic memory

Abstract

Contextual fear conditioning under training conditions involving high stressor intensities has been proposed as an animal model for traumatic memories. The strength of memory for this task has been related to the intensity of the conditioning stressor and post-training corticosterone values. However, administration of a glucocorticoid receptor (GR) antagonist only attenuated memory for this task in rats conditioned at a moderate shock intensity (0.4 mA), but failed to influence conditioning in rats trained at a high shock intensity (1 mA). Here, we further questioned whether interfering with glucocorticoid action at the time of training might be effective in influencing contextual fear conditioning in rats trained under different shock intensities. Rats were subcutaneously injected with the glucocorticoid synthesis inhibitor metyrapone (50, 100 mg/kg) 90 min before being trained in the contextual fear conditioning task, at either 0.4 or 1 mA shock intensities. The results showed that metyrapone, in a dose-dependent manner: (i) attenuated long-term expression of contextual fear conditioning, both in 0.4- and 1 mA-trained rats; and (ii) efficiently prevented increased plasma corticosterone concentration. In addition to further supporting a facilitating role of glucocorticoids in memory consolidation, these findings suggest a critical involvement of these hormones in the formation of traumatic memories.