Stress impairs acquisition of delay eyeblink conditioning in men and women

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Abstract

In rodents stress impairs delay as well as trace eyelid conditioning in females, but enhances it in males. The present study tested the effects of acute psychosocial stress exposure on classical delay eyeblink conditioning in healthy men and women. In a between subject design, participants were exposed to psychosocial stress using the Trier Social Stress Test (TSST) or a control condition which was followed by a delay eyeblink classical conditioning procedure. Stress exposure led to a significant increase in salivary cortisol and impaired acquisition of conditioned eyeblink responses (CRs). This was evident by a later first CR and an overall lower CR rate of the stress group. The stress-induced acquisition impairment was observed in both women and men. Subjects failing to show a stress-induced cortisol increase (cortisol non-responder) were not impaired in acquisition. Our findings indicate that acute stress, possibly via activation of the hypothalamus–pituitary–adrenal (HPA) axis, reduces the ability to acquire a simple conditioned motor response in humans.

Introduction

Stress and its associated activation of the hypothalamus–pituitary–adrenal (HPA) axis is known to influence learning and memory. Glucocorticoids released from the adrenal cortex are important neuroendocrine mediators in this regard. Stress can enhance or impair memory depending on a number of modulatory variables (Conrad, 2005, Diamond et al., 2007, Joels et al., 2006). Effects of stress have been investigated on different forms of memory (Lupien et al., 2007, Roozendaal et al., 2006, Wolf, 2008).

In human subjects, stress effects have so far been established for fear conditioning which is mediated by the amygdala (LaBar & Cabeza, 2006) and for trace eyeblink conditioning which involves hippocampal mechanisms (Cheng et al., 2008, Christian and Thompson, 2003, Woodruff-Pak and Disterhoft, 2008). Stress induced by the cold pressor test led to enhanced trace eyeblink conditioning in healthy men (Duncko, Cornwell, Cui, Merikangas, & Grillon, 2007), while cortisol administration was found to impair trace conditioning in patients with post-traumatic stress disorder (Vythilingam et al., 2006). Moreover, Morbus Cushing patients, who are characterized by substantially elevated endogenous cortisol levels, showed impaired trace conditioning (Grillon, Smith, Haynos, & Nieman, 2004). Stress-induced cortisol elevations or basal cortisol levels were associated with enhanced fear conditioning, especially in men (Jackson et al., 2006, Zorawski et al., 2006, Zorawski et al., 2005), while pharmacologically induced elevated cortisol levels lead to impaired fear conditioning in men (Stark et al., 2006).

Thus, while stress effects have been established for fear conditioning and trace eyeblink in humans, there is as yet no evidence for stress effects on simple delay eyeblink conditioning which have been comprehensively studied in rodents. Delay eyelid conditioning is one of the most widely used conditioning procedures across species (Christian & Thompson, 2003). Stress effects on delay (as well as trace) conditioning in rats were modulated by sex. While male animals showed poorer acquisition under resting condition their performance was enhanced by stress. The opposite pattern was observed in females. Here performance was good under rest but was impaired by stress (Shors, 2004).

Acquisition of delay eyeblink conditioning is dependent upon the functional integrity of cerebellar circuits, while hippocampal damage does not affect CR acquisition or retention (Christian and Thompson, 2003, Daum et al., 1993a, Schugens and Daum, 1999). However, while the hippocampus is not necessary for delay eyelid conditioning per se, pharmacological disruption of normal hippocampal function may adversely affect acquisition (Solomon, Solomon, Schaaf, & Perry, 1983), and hippocampal mechanisms may be critical for the modulatory effects of stress on conditioning in rodents (Bangasser & Shors, 2007).

The present study aimed to assess the effects of psychosocial stress on delay eyeblink conditioning in humans and its potential modulation by sex. Based on the data from rodent studies, acute stress was expected to impair acquisition in women and to enhance acquisition in men.

Section snippets

Participants

A total of 67 young healthy participants were recruited. For the main analysis, only subjects who showed a cortisol increase in response to the stressor (+30 min minus baseline > 0) were included into the stress group. This strategy was chosen in order to ensure a robust HPA response in the stress group and in order to avoid the possibility that the known sex differences in the response to this kind of stressor (Kajantie and Phillips, 2006, Kudielka and Kirschbaum, 2005, Stroud et al., 2002) might

Cortisol level

The cortisol stress responses for female and male subjects are illustrated in Fig. 1. A repeated-measures ANOVA with factors Group (stress versus control), Sex (female versus male) and Time (baseline, +1, +10 and +30 min) yielded a significant Group × Time interaction (F3,147 = 18.48, p < .001). Subsequent paired comparisons revealed significantly higher cortisol levels at 10 min (t51 = 3.09, p = .002) and 30 min (t51 = 3.00, p = .004) after stress compared with the control condition. Stress and control group

Discussion

This study aimed to assess the effects of acute stress on delay eyeblink conditioning in men and women. As expected, psychosocial stress caused a rise in salivary cortisol, accompanied by an increase in negative mood. Acquisition of delay eyeblink conditioning was impaired in the stress group compared to a control condition in both men and women. Stress led to a later occurrence of the first CR and an overall lower CR frequency across acquisition and during extinction, with both the stress and

Acknowledgment

This study was supported by a grant (DA 259/11-1) from the German Research Foundation (DFG).

References (48)

  • B. Roozendaal et al.

    Glucocorticoids interact with emotion-induced noradrenergic activation in influencing different memory functions

    Neuroscience

    (2006)
  • T.J. Shors et al.

    The modulation of Pavlovian memory

    Behavioural Brain Research

    (2000)
  • R. Stark et al.

    Influence of the stress hormone cortisol on fear conditioning in humans: Evidence for sex differences in the response of the prefrontal cortex

    Neuroimage

    (2006)
  • L. Stroud et al.

    Sex differences in stress responses: Social rejection versus achievement stress

    Biological Psychiatry

    (2002)
  • O.T. Wolf

    The influence of stress hormones on emotional memory: Relevance for psychopathology

    Acta Psychologica (Amsterdam)

    (2008)
  • D.S. Woodruff-Pak et al.

    Where is the trace in trace conditioning?

    Trends in Neurosciences

    (2008)
  • D.S. Woodruff-Pak et al.

    Hippocampus in delay eyeblink classical conditioning: Essential for nefiracetam amelioration of learning in older rabbits

    Brain Research

    (1997)
  • D.A. Bangasser et al.

    The hippocampus is necessary for enhancements and impairments of learning following stress

    Nature Neuroscience

    (2007)
  • C. Bellebaum et al.

    Effects of age and awareness on eyeblink conditional discrimination learning

    Behavioral Neuroscience

    (2004)
  • T.W. Buchanan et al.

    Impaired memory retrieval correlates with individual differences in cortisol response but not autonomic response

    Learning & Memory

    (2006)
  • L. Cahill

    Why sex matters for neuroscience

    Nature Reviews Neuroscience

    (2006)
  • D.T. Cheng et al.

    Neural substrates underlying human delay and trace eyeblink conditioning

    Proceedings of the National Academy of Sciences of the United States of America

    (2008)
  • K.M. Christian et al.

    Neural substrates of eyeblink conditioning: Acquisition and retention

    Learning & Memory

    (2003)
  • R.E. Clark et al.

    Trace and delay eyeblink conditioning: Contrasting phenomena of declarative and nondeclarative memory

    Psychological Science

    (2001)
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