Chronic stress enhances ibotenic acid-induced damage selectively within the hippocampal CA3 region of male, but not female rats

doi:10.1016/j.neuroscience.2004.01.049

Neuroscience

Volume 125, Issue 3, 2004, Pages 759-767

https://doi.org/10.1016/j.neuroscience.2004.01.049 Get rights and content

Abstract

The purpose of this investigation was to assess the ability of the hippocampus to withstand a metabolic challenge following chronic stress. An N-methyl-d-aspartate receptor excitotoxin (ibotenic acid, IBO) was infused into the CA3 region of the hippocampus following a period of restraint for 6 h/day/21 days. Following the end of restraint when CA3 dendritic retraction persists (3 to 4 days), rats were infused with IBO (or vehicle) into the CA3 region of the hippocampus. Stressed male rats showed significantly more CA3 damage after IBO infusion relative to controls and the saline-infused side. Moreover, IBO-exacerbation of damage in males was not observed in the CA3 region 3 to 4 days after acute stress (6 h restraint), nor in the CA1 region after chronic stress. Females were also examined and chronic stress did not exacerbate IBO damage in the CA3 region. Overall, these results demonstrate that chronic stress compromises the ability of the hippocampus to withstand a metabolic challenge days after the chronic stress regimen has subsided in male rats. Whether the conditions surrounding CA3 dendritic retraction in females represents vulnerability is less clear and warrants further investigation.

Section snippets

Subjects

Arizona State University's Institutional Animal Care and Use Committee approved all procedures, in accordance with the applicable portions of the Animal Welfare Act and “Guide for the Care and Use of Laboratory Animals” by Department of Health and Human Resources. All efforts were made to minimize the number of animals used and their suffering. Male (n=64) and female (n=36) Sprague–Dawley rats (Charles River, Hartford, CT, USA) were same sex, pair-housed in temperature and light-controlled

Results

Based upon the section containing the needle tip, nine pairings were made between control and stressed rats with similar needle placements and percentage of CA3 damage (Fig. 2). One control and five stressed rats were not paired because the location of the needle tip and/or the amount of CA3 damage at the needle tip differed by more than 10%. Rats with less than 20% CA3 damage at the needle tip had poor needle placements (lateral, medial, etc.) and were removed from the analysis. Of the paired

Discussion

These results support the view that chronic restraint selectively compromises the hippocampal CA3 region in young adult males. IBO damaged more neurons in the CA3 region of chronically stressed males compared to the contralateral, vehicle-infused side and to IBO-infused controls. To determine whether these effects of chronic restraint were widespread within the hippocampus, CA1 damage after IBO infusion was investigated and found to be similar between chronically stressed males and controls.

Acknowledgements

This work was funded by MH64727 (Conrad), a research incentive award from ASU College of Liberal Arts and Sciences (Conrad), and the Howard Hughes Medical Institute through the Undergraduate Biology Enrichment Program (Jackson and Wise). Preliminary data were presented at the 32^nd Annual Meeting of the Society for Neuroscience in November 2002. The contributions of following individuals are gratefully acknowledged: Sarah Baran, Rudy Bellani, Angelique Ferayorni, George G. Gifford, Katherine A.