Role of the endocannabinoid system in regulating glucocorticoid effects on memory for emotional experiences

Glucocorticoids, stress hormones released from the adrenal cortex, have potent modulatory effects on emotional memory. Whereas early studies focused mostly on the detrimental effects of chronic stress and glucocorticoid exposure on cognitive performance and the classic genomic pathways that mediate these effects, recent findings indicate that glucocorticoids exert complex and often rapid influences on distinct memory phases. Specifically, glucocorticoids have been shown to enhance memory consolidation of emotionally arousing experiences, but to impair memory retrieval and working memory during emotionally arousing test situations. Furthermore, growing evidence indicates that these different glucocorticoid effects depend on a nongenomically mediated interaction with emotional arousal-induced noradrenergic activation within the basolateral complex of the amygdala. In this paper, we present a model suggesting that the endocannabinoid system, a lipid-based retrograde signaling system, might play an important role in mediating such rapid glucocorticoid influences on the noradrenergic system in modulating memory of emotionally arousing experiences.