Inhibition of cortisol production by metyrapone enhances trace, but not delay, eyeblink conditioning

Nees, Frauke; Richter, Steffen; Lass‐Hennemann, Johanna; Blumenthal, Terry D.; Schächinger, Hartmut

doi:10.1007/s00213-008-1155-2

Cited by 13 publications

(7 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…If corticosterone’s effects are mediated by hippocampus, we should see deficits similar to those reported by Ivkovich and Stanton (2001) where hippocampal lesions on postnatal day 10 impaired subsequent trace eyeblink conditioning on Days 25–26 but not delay eyeblink conditioning at matching inter-stimulus intervals. In humans with hyper cortisolism, trace eyeblink conditioning deficits were observed (Grillon et al, 2004) while metyrapone- induced acute, mild hypo cortisolism facilitated trace but not delay eyeblink conditioning (Nees et al, 2008), confirming that the trace eyeblink conditioning task may be sensitive to glucocorticoid effects mediated by hippocampus.…”

Section: 0 Introductionmentioning

confidence: 84%

“…For example, intra-hippocampal infusion of corticosterone improves memory consolidation in awake but not sleeping rats (Kelemen et al, 2014). Memory consolidation is impaired in the absence of glucocorticoids following adrenalectomy or administration of antagonists (e.g., Marin et al, 2011; Nees et al, 2008). In contrast, prolonged exposure to stressors activates GRs, which appears to impair hippocampal excitability associated with learning plasticity, altering NMDA receptor expression (Lee et al, 2003), suppressing LTP, and impairing performance on declarative and spatial memory tasks and memory retrieval (see reviews: Conrad et al, 2005; DeKloet et al, 1999; McEwen et al, 2006, 2007; Roosendaal, 2002).…”

Section: 0 General Discussionmentioning

confidence: 99%

“…When cortisol levels are endogenously high (Cushing’s syndrome) trace eyeblink conditioning is impaired and correlates with hippocampal-declarative memory deficits (Grillon et al, 2004). On the other hand, when cortisol production was inhibited by metyrapone in healthy volunteers, facilitation of trace eyeblink conditioning was observed while delay conditioning remained unaffected (Nees et al, 2008). It is possible that the later, but not earlier, postnatal glucocorticoid effects on cognition are mediated by hippocampus, especially since the immediate post-SHRP period of PND 15–18 has been reported as a time when there is a noticeable spurt in hippocampal cell maturation, in particular in the dentate gyrus (Bayer & Altman, 1974).…”

Section: 0 General Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Influence of postnatal glucocorticoids on hippocampal-dependent learning varies with elevation patterns and administration methods

Claflin

Schmidt

Vallandingham

et al. 2017

Neurobiology of Learning and Memory

View full text Add to dashboard Cite

Recent interest in the lasting effects of early-life stress has expanded to include effects on cognitive performance. An increase in circulating glucocorticoids is induced by stress exposure and glucocorticoid effects on the hippocampus likely underlie many of the cognitive consequences. Here we review studies showing that corticosterone administered to young rats at the conclusion of the stress-hyporesponsiveness period affects later performance in hippocampally-mediated trace eyeblink conditioning. The nature and even direction of these effects varies with the elevation patterns (level, duration, temporal fluctuation) achieved by different administration methods. We present new time course data indicating that constant glucocorticoid elevations generally corresponded with hippocampus-mediated learning deficits, whereas acute, cyclical elevations corresponded with improved initial acquisition. Sensitivity was greater for males than for females. Further, changes in hippocampal neurogenesis paralleled some but not all effects. The findings demonstrate that specific patterns of glucocorticoid elevation produced by different drug administration procedures can have markedly different, sex-specific consequences on basic cognitive performance and underlying hippocampal physiology. Implications of these findings for glucocorticoid medications prescribed in childhood are discussed.

show abstract

Section: 0 Introductionmentioning

confidence: 84%

Section: 0 General Discussionmentioning

confidence: 99%

Section: 0 General Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Influence of postnatal glucocorticoids on hippocampal-dependent learning varies with elevation patterns and administration methods

Claflin

Schmidt

Vallandingham

et al. 2017

Neurobiology of Learning and Memory

View full text Add to dashboard Cite

show abstract

“…In humans, cortisol administration (Kuehl et al, 2010) or endogenous secreted cortisol by social stress (Duncko et al, 2007) enhanced performance on a trace eye-blink-conditioning task in men. But another study found impairment by cortisol administration in both men and women (Nees et al, 2008), or even no effect at all (Vythilingam et al, 2006). These contradictions notwithstanding, it is important to realize that within the context of etiological models of anxiety disorders sex specific sensitivity to stressful events has been repeatedly associated with the higher prevalence of mood and anxiety disorders in women (Kessler et al, 1993; Trentani et al, 2003; Cahill, 2006).…”

Section: Introductionmentioning

confidence: 99%

Contextual control over expression of fear is affected by cortisol

Ast¹,

Vervliet²,

Kindt³

2012

Front. Behav. Neurosci.

View full text Add to dashboard Cite

At the core of anxiety disorders is the inability to use contextual information to modulate behavioral responses to potentially threatening events. Models of the pathogenesis of anxiety disorders incorporate stress and concomitant stress hormones as important vulnerability factors, while others emphasize sex as an important factor. However, translational basic research has not yet investigated the effects of stress hormones and sex on the ability to use contextual information to modulate responses to threat. Therefore, the purpose of the present study was threefold: first, we aimed at developing an experimental paradigm specifically capable of capturing contextual modulation of the expression of fear. Second, we tested whether cortisol would alter the contextualization of fear expression. Third, we aimed at assessing whether alterations in contextualization due to cortisol were different for men and women. Healthy participants (n = 42) received placebo or hydrocortisone (20 mg) prior to undergoing a newly developed differential contextual fear-conditioning paradigm. The results indicated that people rapidly acquire differential contextual modulation of the expression of fear, as measured by fear potentiated startle (FPS) and skin conductance responses (SCR). In addition, cortisol impaired the contextualization of fear expression leading to increased fear generalization on FPS data in women. The opposite pattern was found in men. Finally, as assessed by SCR, cortisol impaired differential conditioning in men. The results are in line with models suggesting heightened vulnerability in women for developing anxiety disorders after stressful events.

show abstract

“…Furthermore, the 500-ms dark period between successive light stimuli resembles task characteristics of trace classical eyeblink conditioning, in which hippocampus functions are mandatory (Clark and Squire 1998) and which is sensitive to glucocorticoid modulation (Grillon et al 2004;Nees et al 2008;Nees et al 2010). Interestingly, contingency knowledge is required to produce effective trace eyeblink conditioning (Clark and Squire 1998), but no such contingency knowledge seems to be necessary for implicit sequence learning to occur.…”

Section: Discussionmentioning

confidence: 94%