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Cited by 224Stress Responses and CortisolMemory and Neural MechanismsEstrogen and related hormone effects

Effects of chronic restraint stress and estradiol on open field activity, spatial memory, and monoaminergic neurotransmitters in ovariectomized rats

Bowman, R.E, Ferguson, D, Luine, V.N·2002·Neuroscience
DOI 10.1016/s0306-4522(02)00156-2
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Abstract

Twenty-one days of chronic restraint stress impairs male rat performance on the radial arm maze [Luine et al. (1994) Brain Res. 639, 167-170], but enhances female rat performance [Bowman et al. (2001) Brain Res. 904, 279-289]. To assess possible ovarian hormone mechanisms underlying this sexually dimorphic response to stress, we examined chronic stress effects in ovariectomized rats. Ovariectomized rats received Silastic capsule implants containing cholesterol or estradiol and were assigned to a daily restraint stress (21 days, 6 h/day) or non-stress group. Following the stress period, subjects were tested for open field activity and radial arm maze performance. Stress and estradiol treatment affected open field activity. All stressed animals, with or without estradiol treatment, made fewer total outer sector crossings. In contrast, estradiol-treated animals, with or without stress, made more inner sector visits, an indication that estradiol decreased anxious behavior on the open field across time. As measured by the total number of visits required to complete the task, stress did not affect radial arm maze performance in ovariectomized rats, but estradiol-treated animals, with or without stress, performed better than non-treated animals on the radial arm maze. Stressed subjects receiving estradiol showed the best radial arm maze performance. Following killing, tissue samples were obtained from various brain regions known to contribute to learning and memory, and monoamine and metabolite levels were measured. Several changes were observed in response to both stress and estradiol. Most noteworthy, stress treatment decreased homovanillic acid levels in the prefrontal cortex, an effect not previously observed in stressed intact females. Estradiol treatment increased norepinephrine levels in CA3 region of the hippocampus, mitigating stress-dependent changes. Both stress and estradiol decreased dentate gyrus levels of 5-hydroxyindole acetic acid. In summary, the current study provides novel information showing that estradiol alters behavioral and neurochemical responses to stress in ovariectomized rats. Estradiol treatment decreased anxious behavior on the open field and stressed animals receiving estradiol had enhanced radial arm maze performance. In relation to interactions between stress and estradiol on cognition and anxiety, changes in the prefrontal cortex dopaminergic system, dentate gyrus serotonergic system, and norepinephrine levels in the CA3 region appear important. Results show that estradiol may moderate stress effects on cognition and anxiety through both organizational and activation effects.

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  • Removal of ovarian hormones in rodents decreases the pro-depressant or anxiogenic effects of stress while simultaneously increasing the negative effects of stress on spatial and non-spatial memory.

    “removal of ovarian hormones decreases the pro–depressant or anxiogenic effects of stress, while simultaneously increasing the negative effects of stress on spatial and non–spatial memory85, 91, 92”

    From Neurobiology of resilience (2012) · cites this paper as [92]

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Authors
Bowman, R. E., Ferguson, D., & Luine, V. N.
Affiliations
  • The Graduate Center, CUNY (US)
  • City University of New York (US)
Corresponding author
Bowman, R.E
ORCID
Venue
Neuroscience
Publisher
Elsevier BV
Published
2002-08
Volume
113
Issue
2
Pages
401-410
ISSN
0306-4522 (ISSN-L)
DOI
10.1016/s0306-4522(02)00156-2
OpenAlex
W2060908340
Cited by
224
References
65
Citations by year
2026: 2 · 2025: 2 · 2022: 5 · 2021: 6 · 2020: 7 · 2019: 5 · 2018: 9 · 2017: 13 · 2016: 4 · 2015: 12 · 2014: 14 · 2013: 16 · 2012: 9
FWCI
4.68
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5f31mh012515-03)
  • National Institute of Mental Health (1F31MH12515)
Topics
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
Keywords
chronic restraint stress, estradiol, ovariectomy, spatial memory, anxiety, open field behavior, radial maze, monoamines, homovanillic acid, norepinephrine, 5-hydroxyindoleacetic acid, prefrontal cortex, hippocampal CA3, dentate gyrus, sex differences, stress hormones
MeSH terms
Animals, Body Weight, Brain, Estradiol, Female, Memory, Motor Activity, Ovariectomy, Restraint, Physical, Space Perception, Stress, Physiological, Biogenic Monoamines, Rats, Sprague-Dawley, Neurotransmitter Agents, Maze Learning, Rats

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