Elsevier

Neuroscience

Volume 204, 1 March 2012, Pages 104-116
Neuroscience

Endocannabinoid Signaling as a Mediator of the Effects of Stress
Role of the endocannabinoid system in regulating glucocorticoid effects on memory for emotional experiences

https://doi.org/10.1016/j.neuroscience.2011.08.047Get rights and content

Abstract

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.

This article is part of a Special Issue entitled: Stress, Emotional Behavior and the Endocannabinoid System.

Highlights

▶Glucocorticoid effects on memory require emotion-induced noradrenergic activity. ▶Such glucocorticoid actions are mediated by rapid nongenomic mechanisms. ▶Endocannabinoids might be essential in mediating these rapid glucocorticoid effects.

Section snippets

Glucocorticoid effects on different memory phases: dependence on arousal status

In this section, we describe the effects of glucocorticoids on different memory phases and their interaction with emotional arousal. There is compelling evidence from studies in both animals and humans that glucocorticoids are involved in regulating the consolidation of memory processes (Flood et al., 1978, de Kloet, 2000; Roozendaal, 2000, Roozendaal, 2002; McGaugh and Roozendaal, 2002, Het et al., 2005; Sandi and Pinelo-Nava, 2007, de Quervain et al., 2009, Roozendaal et al., 2009). Memory

Glucocorticoid interactions with arousal-induced noradrenergic activation in the basolateral amygdala

Why do glucocorticoids only modulate memory of emotionally arousing experiences? Our findings suggest that interactions between stress hormones and noradrenergic activity within the amygdala may be key in determining this selectivity. It is well established that emotional experiences that induce the release of adrenal stress hormones also increase amygdala neuronal activity (Pelletier et al., 2005). Extensive evidence from our as well as other laboratories indicates that the enhancing effects

Rapid nongenomic glucocorticoid effects: involvement of the endocannabinoid system

Glucocorticoids are known to modulate cellular function, including learning and memory, through both genomic (slow) and nongenomic (rapid) pathways (de Kloet, 2000, Dallman, 2005). Genomic glucocorticoid effects are mediated by classical steroid mechanisms involving transcriptional regulation. Glucocorticoids can influence transcription through both DNA-binding–dependent and DNA-binding–independent mechanisms (de Kloet, 2000). Although many glucocorticoid actions suit the time frame for a

Role of endocannabinoids in regulating glucocorticoid effects on memory: the model

Endocannabinoid signaling is crucial for certain forms of short- and long-term synaptic plasticity at excitatory and inhibitory synapses, and thereby contributes to various aspects of brain function, including learning and memory (Kano et al., 2009). It has long been recognized, in animals and humans, that endocannabinoids influence different memory phases. Behavioral studies in humans indicate that cannabis consumption as well as synthetic CB1 receptor agonists impair cognitive processes that

Conclusions and future directions

The findings summarized previously indicate that glucocorticoids enhance memory consolidation for emotionally arousing experiences and impair memory retrieval and working memory during emotionally arousing test situations via rapid interactions with arousal-induced noradrenergic mechanisms. The endocannabinoid system might play a crucial role in mediating such rapid glucocorticoid effects on the noradrenergic system. However, there are many fascinating, unanswered questions. First, our model

Acknowledgments

Research was supported by a Jan Kornelis de Cock Foundation Research Grant to P.A. and “Progretti di Ricerca 2010” (Sapienza University of Rome) to P.C.

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