The effects of sex and hormonal status on restraint-stress-induced working memory impairment - PubMed (original) (raw)

The effects of sex and hormonal status on restraint-stress-induced working memory impairment

Rebecca M Shansky et al. Behav Brain Funct. 2006.

Abstract

Background: Restraint stress has been shown to elicit numerous effects on hippocampal function and neuronal morphology, as well as to induce dendritic remodeling in the prefrontal cortex (PFC). However, the effects of acute restraint stress on PFC cognitive function have not been investigated, despite substantial evidence that the PFC malfunctions in many stress-related disorders.

Methods: The present study examined the effects of restraint stress on PFC function in both male rats and cycling female rats in either the proestrus (high estrogen) or estrus (low estrogen) phase of the estrus cycle. Animals were restrained for 60 or 120 minutes and then tested on spatial delayed alternation, a PFC-mediated task. Performance after stress was compared to performance on a different day under no-stress conditions, and analyzed using analysis of variance (ANOVA).

Results: Sixty minutes of restraint impaired only females in proestrus, while 120 minutes of restraint produced significant impairments in all animals. Increases in task completion times did not affect performance.

Conclusion: These results demonstrate an interaction between hormonal status and cognitive response to stress in female rats, with high estrogen levels being associated with amplified sensitivity to stress. This effect has been previously observed after administration of a pharmacological stressor (the benzodiazepine inverse agonist FG7142), and results from both studies may be relevant to the increased prevalence of stress-related disorders, such as major depressive disorder, in cycling women. Overall, the results show that restraint stress has important effects on the cognitive functions of the PFC, and that hormonal influences in the PFC are an important area for future research.

PubMed Disclaimer

Figures

Figure 1

Figure 1

Representative Training Schedule. Rats were tested daily, Monday through Friday. In order to be eligible for stress testing, three criteria must be met: 1) The animal must have achieved a score of 6, 7 or 8 (out of 10) for at least two consutive days; 2) at least one week must have passed since the last stress exposure; 3) females must be cycling regularly on a 4–5 day cycle, and it must be anticipated that they will be in either proestrus or estrus on stress day. In this figure, the rat is ready for testing on the first Wednesday because her two previous scores are 7 and 8, and she will be in estrus. In the sond week, she does not receive stress treatment because her scores do not qualify her on a day when she will be in estrus or proestrus. In the third week, her scores on Tuesday and Wednesday qualify her for treatment on Thursday, and she will be in proestrus, so she receives treatment. In week four, her scores and cycle qualify her for treatment on Friday.

Figure 2

Figure 2

Females in proestrus are more sensitive to the PFC-impairing effects of stress than males or females in estrus. Animals were restrained for 0, 60 or 120 min prior to testing on the delayed alternation T-maze task. Results are represented as mean +/- SEM number correct. Mean scores after 0, 60 and 120 min restraint were 7.4 +/- .22, 7.6 +/- .3 and 5.7 +/- .51 for males; 7.1 +/- .18, 7.4 +/- .4 and 5.9 +/- .51 for females in estrus; and 6.9 +/- .2, 5 +/- .35 and 5.9 +/- .5 for females in proestrus. * = significantly different from self in control conditions, p < .05, ** = p < .005, *** = p < .0005, † = significantly different from self during estrus, p < .02.

Figure 3

Figure 3

Group differences in time were observed, but they did not correlate with differences in performance. Task completion times were recorded for all groups. Results are represented as mean +/- SEM minutes to finish. Mean task completion times (in minutes) after 0, 60 and 120 min were 1.8 +/- .4, 4.5 +/- 1.1 and 5 +/- 1 for males; 4.3 +/- .5, 5.8 +/- .7 and 4.8 +/- .64 for females in estrus; and 4.7 +/- 1.6, 5.3 +/- .6 and 3.9 +/- .4 for females in proestrus. * = significantly different from all other groups.

Similar articles

Cited by

References

    1. Yamada K, McEwen BS, Pavlides C. Site and time dependent effects of acute stress on hippocampal long-term potentiation in freely behaving rats. Experiemental Brain Research. 2003;152:52–59. doi: 10.1007/s00221-003-1519-0. - DOI - PubMed
    1. Pham K, Nacher J, Hof PR, McEwen BS. Repeated restraint stress suppresses neurogenesis and induces biphasic PSA-NCAM expression in the adult rat dentate gyrus. European Journal of Neuroscience. 2003;17:879–886. doi: 10.1046/j.1460-9568.2003.02513.x. - DOI - PubMed
    1. McEwen BS. Plasticity of the hippocampus: adaptation to chronic stress and allostatic load. Ann N Y Acad Sci. 2001;933:265–277. - PubMed
    1. Radley JJ, Sisti HM, Hao J, Rocher AB, McCall T, Hof PR, McEwen BS, Morrison JH. Chronic behavioral stress induces apical dendritic reorganization in pyramidal neurons of the medial prefrontal cortex. Neuroscience. 2004;125:1–6. doi: 10.1016/j.neuroscience.2004.01.006. - DOI - PubMed
    1. Cook SC, Wellman CL. Chronic stress alters dendritic morphology in rat medial prefrontal cortex. J Neurobiol. 2004;60:236–248. doi: 10.1002/neu.20025. - DOI - PubMed

LinkOut - more resources