ReviewGlucocorticoids and the regulation of memory in health and disease
Introduction
Stress activates the hypothalamus–pituitary–adrenal axis, which results in the release of glucocorticoid hormones (cortisol in humans, corticosterone in rodents) from the adrenal cortex. It has long been recognized that glucocorticoids readily enter the brain and affect cognition. Early reports on both enhancing and impairing properties of glucocorticoids on memory [9], [16], [21], [63], [91] have indicated that these hormones have complex effects on cognitive functions. More recent studies investigating glucocorticoid effects on distinct memory phases and studies discerning acute from chronic effects helped to disentangle the multifaceted actions of these stress hormones. For example, acute elevations of glucocorticoids are known to enhance the consolidation of memory of new information, but to impair the retrieval of already stored information [51], [146], [156]. Conditions with chronically elevated glucocorticoid levels are usually associated with impaired cognitive performance and these deficits are thought to result from a cumulative and long-lasting burden on hippocampal function and morphology [102], [172]. Recently, however, it became clear that memory deficits observed under such chronic conditions can also result, at least in part, from acute and reversible glucocorticoid actions on memory retrieval processes [39].
In the present review, we will summarize and discuss how glucocorticoids affect memory consolidation, retrieval and working memory and why these stress hormones specifically modulate memory of emotionally arousing experiences. Furthermore, because emotional memory plays a crucial role in the pathogenesis and symptomatology of anxiety disorders, such as posttraumatic stress disorder (PTSD) or phobias, we will discuss to what extent the basic findings on glucocorticoid effects on emotional memory might have clinical implications.
Section snippets
Glucocorticoid effects on memory consolidation
Memory consolidation is the process by which a fragile short-term memory trace is transferred into stable long-term memory. However, not all information is equally well transferred into long-term storage. In fact, it is well recognized that especially emotionally arousing experiences are well remembered, even after decades [107]. Successful memory consolidation depends on de-novo protein synthesis and on long-term changes in synaptic plasticity [76]. There is extensive evidence that
Glucocorticoid effects on memory retrieval
Studies showing that stress induces memory impairment when retention is tested shortly after learning (before memory consolidation took place) and glucocorticoid levels are still elevated [54], [81], indicated that glucocorticoids possibly interfere with memory retrieval processes. In the first study investigating the specific effects of stress and glucocorticoids on memory retrieval [51], we reported that 30 min after exposure to footshock stress, rats had impaired retrieval of spatial memory
Glucocorticoid effects on working memory
Working memory is a dynamic process whereby information is updated continuously, providing a temporary storage of information [12], [75]. Evidence from lesion, pharmacological, imaging and clinical studies indicates that working memory depends on the integrity of the prefrontal cortex [23], [66], [126]. Stress exposure is known to impair performance of rats on a delayed alternation task, a task commonly used to assess working memory in rodents [11]. Basal levels of endogenous glucocorticoids
Modulatory effects of glucocorticoids on emotional memory: implications for anxiety disorders
From the findings reviewed above we have learned that glucocorticoids enhance memory consolidation but impair memory retrieval and working memory in emotionally arousing situations (Fig. 4). Enhanced memory for emotional events is a well-recognized phenomenon, which helps us to remember important information. Although glucocorticoid-induced temporary impairments of memory retrieval and working memory are certainly unwanted in exam situations, these effects should not a priori be regarded as
Conclusion
In the present paper we have reviewed evidence from both animal and human studies, which indicated that glucocorticoids enhance memory consolidation but impair memory retrieval and working memory (Fig. 4). Importantly, these hormone effects depend on emotional arousal-induced activation of noradrenergic transmission within the BLA and on interactions of the BLA with other brain regions, such as the hippocampus and neocortical regions. Therefore, glucocorticoids, via BLA activation, can modulate
References (210)
- et al.
Endogenous cortisol elevations are related to memory facilitation only in individuals who are emotionally aroused
Psychoneuroendocrinology
(2006) - et al.
Administration of corticosterone after memory reactivation disrupts subsequent retrieval of a contextual conditioned fear memory: dependence upon training intensity
Neurobiol. Learn. Mem.
(2008) - et al.
The effects of long-term corticosterone administration on hippocampal morphology and cognitive performance of middle-aged rats
Brain Res.
(1994) - et al.
Behavioral effects of metyrapone on Pavlovian extinction
Neurosci. Lett.
(2004) - et al.
Steroid hormone receptors: many actors in search of a plot
Cell
(1995) - et al.
Dose-dependent effects of hydrocortisone on memory in human males
Physiol. Behav.
(1986) - et al.
Learning under stress: a role for the neural cell adhesion molecule NCAM
Neurobiol. Learn. Mem.
(2009) - et al.
Adrenocortical hormones and avoidance behaviour of rats
Int. J. Neuropharmacol.
(1968) A cognitive neuroscience account of posttraumatic stress disorder and its treatment
Behav. Res. Ther.
(2001)- et al.
Hippocampal volume, spectroscopy, cognition, and mood in patients receiving corticosteroid therapy
Biol. Psychiatry
(2004)
Exogenous cortisol exerts effects on the startle reflex independent of emotional modulation
Pharmacol. Biochem. Behav.
Enhanced memory for emotional material following stress-level cortisol treatment in humans
Psychoneuroendocrinology
Autobiographic memory impairment following acute cortisol administration
Psychoneuroendocrinology
Induction of the c-fos proto-oncogene in rat amygdala during unconditioned and conditioned fear
Brain Res.
Low-dose hydrocortisone in chronic fatigue syndrome: a randomised crossover trial
Lancet
Influence of chronic corticosterone and glucocorticoid receptor antagonism in the amygdala on fear conditioning
Neurobiol. Learn. Mem.
Fast glucocorticoid actions on brain: back to the future
Front. Neuroendocrinol.
Anxiety and affective style: role of prefrontal cortex and amygdala
Biol. Psychiatry
Plasma catecholamine, corticosterone and glucose responses to repeated stress in rats: effect of interstressor interval length
Physiol. Behav.
Stress and cognition: are corticosteroids good or bad guys?
Trends Neurosci.
Initial posttraumatic urinary cortisol levels predict subsequent PTSD symptoms in motor vehicle accident victims
Biol. Psychiatry
An fMRI investigation of memory encoding in PTSD: influence of symptom severity
Neuropsychologia
Glucocorticoid receptor antagonism in the basolateral amygdala and ventral hippocampus interferes with long-term memory of contextual fear
Behav. Brain Res.
Thought suppression: specificity in agoraphobia versus broad impairment in social phobia?
Behav. Res. Ther.
Memory facilitating and anti-amnesic effects of corticosteroids
Pharmacol. Biochem. Behav.
The prefrontal cortex and its relation to behavior
Prog. Brain Res.
Norepinephrine release in the amygdala in response to footshock stimulation
Neurobiol. Learn. Mem.
Facilitation of time-dependent memory processes with posttrial epinephrine injections
Behav. Biol.
A meta-analytic review of the effects of acute cortisol administration on human memory
Psychoneuroendocrinology
Stress- and treatment-induced elevations of cortisol levels associated with impaired declarative memory in healthy adults
Life Sci.
Dose-dependent action of corticosteroids on brain serotonin content and passive avoidance behavior
Horm. Behav.
Effects of oral cortisol treatment in healthy young women on memory retrieval of negative and neutral words
Neurobiol. Learn. Mem.
A non-arousing test situation abolishes the impairing effects of cortisol on delayed memory retrieval in healthy women
Neurosci. Lett.
Adrenocortical suppression blocks the enhancement of memory storage produced by exposure to psychological stress in rats
Brain Res.
Effects of chronic corticosterone ingestion on spatial memory performance and hippocampal serotonergic function
Brain Res.
Electrolytic lesions of the fimbria/fornix, dorsal hippocampus, or entorhinal cortex produce anterograde deficits in contextual fear conditioning in rats
Neurobiol. Learn. Mem.
Organization of amygdaloid projections to the prefrontal cortex and associated striatum in the rat
Neuroscience
Acute cortisol elevations cause heightened arousal ratings of objectively nonarousing stimuli
Emotion
Cortisol variation in humans affects memory for emotionally laden and neutral information
Behav. Neurosci.
Impaired declarative memory for emotional material following bilateral amygdala damage in humans
Learn. Mem.
Low-dose cortisol for symptoms of posttraumatic stress disorder
Am. J. Psychiatry
Medial prefrontal cortex determines how stressor controllability affects behavior and dorsal raphe nucleus
Nat. Neurosci.
Amygdala response in patients with acute PTSD to masked and unmasked emotional facial expressions
Am. J. Psychiatry
Noise stress impairs prefrontal cortical cognitive function in monkeys: evidence for a hyperdopaminergic mechanism
Arch. Gen. Psychiatry
Working memory
Science
Specific and Social Phobias
Cortisol activity and cognitive changes in psychotic major depression
Am. J. Psychiatry
Memory functions in prednisone-treated kidney transplant patients
Clin. Transplant.
Clinical correlates of 24-h cortisol and norepinephrine excretion among subjects seeking treatment following the world trade center attacks on 9/11
Ann. N.Y. Acad. Sci.
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