Sex Differences in Chronic Stress Effects on Memory in Rats
Open accessAbstract
Recent studies in rodent models and in humans have shown that the status of both the gonadal and adrenal axes (hypothalamic-pituitary-gonadal, HPG and hypothalamic-pituitary-adrenal, HPA, respectively) can influence learning and memory function. In this article, the effects of activating the HPA axis (stress) on performance of memory tasks in rats are reviewed. More importantly, results are presented which show that chronic stress has a different impact on performance of these tasks depending upon the sex of the rat. These observations are novel and potentially important since few studies, animal or human, have utilized females as subjects in studies of the stress response. Sex differences in the effects of chronic stress on memory were investigated in rats using an object recognition task and two spatial memory tasks, radial arm maze and object location. Given the same chronic stress--21 days of restraint for 6 h each day--males were impaired in all of the memory tests while females showed enhanced performance of the spatial memory tasks and no changes in object recognition performance. Levels of neurotransmitters and metabolites were measured in brain areas important for cognition in the subjects in order to determine neural systems that may respond to stress and mediate the cognitive responses. These results show that responses of monoamine and amino acid containing neural systems may contribute to or underlie sex differences in stress effects on cognition. Stress decreased dopaminergic activity in the frontal cortex and amygdala of males but not females; whereas, in CA3 of the hippocampus, stress increased levels of 5-HT and norepinephrine in females, but not males, and increased GABA in males, but not females. Finally, a possible role for estradiol in mediating sexually differentiated responses to stress was examined. Behavioral and neurochemical evaluations in ovariectomized, stressed females, with or without estrogen replacement, suggest that sex differences in response to stress are influenced by both the organizing and activating effects of estradiol. A few, recent studies in humans, that show sexually dimorphic relationships between chronic stress and cognition, are also highlighted. These results in humans are consistent with the pattern of results in rats. Clearly, further studies are necessary to substantiate sex differences in stress effects on memory function in humans and to understand mechanisms whereby estrogen may influence the stress response in rats. Nonetheless, recent studies show sexually differentiated cognitive responses to chronic stress and underline the importance of considering the sex/gender of subjects when studying the stress response.
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Female rodents tend to be more susceptible to stress-induced dysfunction in emotional domains but show greater stress resilience in cognitive domains.
“while female rodents tend to be more susceptible to stress–induced dysfunction in emotional domains (i.e., sucrose preference and forced swim test), they tend to show a greater degree of stress resilience in cognitive domains (i.e., object placement and recognition) (for review see51).”
From Neurobiology of resilience (2012) · cites this paper as [51]
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Cites
Neurocircuitry of stress: central control of the hypothalamo–pituitary–adrenocortical axis
Herman, J. P., & Cullinan, W. E. (1997) · Trends in Neurosciences · doi:10.1016/s0166-2236(96)10069-2 · Cited by 2,270 · see citing works
Kirschbaum, C., Kudielka, B. M., Gaab, J., Schommer, N. C., & Hellhammer, D. H. (1999) · Psychosomatic Medicine · doi:10.1097/00006842-199903000-00006 · Cited by 1,890 · cited 1× · see citing works
“When exposed to a brief psychosocial stress, the Trier Social Stress Test, luteal phase women and men showed higher salivary cortisol levels than follicle phase women and women on oral contraceptives (Kirschbaum et al., 1999).”
Estrogen Actions in the Central Nervous System
McEwen, B. S., & Alves, S. E. (1999) · Endocrine Reviews · doi:10.1210/edrv.20.3.0365 · Cited by 1,483 · see citing works
Stress induces atrophy of apical dendrites of hippocampal CA3 pyramidal neurons
Watanabe, Y., Gould, E., & McEwen, B. S. (1992) · Brain Research · doi:10.1016/0006-8993(92)91597-8 · Cited by 1,212 · see citing works
Repeated stress causes reversible impairments of spatial memory performance.
Luine, V., Villegas, M., Martinez, C., & McEwen, B. (1994) · Brain Research · doi:10.1016/0006-8993(94)91778-7 · Cited by 813 · see citing works
Self-citationZahrt, J., Taylor, J. R., Mathew, R. G., & Arnsten, A. F. T. (1997) · The Journal of Neuroscience · doi:10.1523/jneurosci.17-21-08528.1997 · Cited by 796 · see citing works
Gonadal Steroid Hormone Receptors and Sex Differences in the Hypothalamo-Pituitary-Adrenal Axis
Handa, R. J., Burgess, L. H., Kerr, J. E., & O'Keefe, J. A. (1994) · Hormones and Behavior · doi:10.1006/hbeh.1994.1044 · Cited by 793 · see citing works
Conrad, C. D., Galea, L. A. M., Kuroda, Y., & McEwen, B. S. (1996) · Behavioral Neuroscience · doi:10.1037/0735-7044.110.6.1321 · Cited by 784 · see citing works
VIAU, V., & MEANEY, M. J. (1991) · Endocrinology · doi:10.1210/endo-129-5-2503 · Cited by 666 · see citing works
Beatty, W. W. (1979) · Hormones and Behavior · doi:10.1016/0018-506x(79)90017-5 · Cited by 631 · see citing works
Murphy, B. L., Arnsten, A. F., Goldman-Rakic, P. S., & Roth, R. H. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.3.1325 · Cited by 590 · see citing works
Chronic stress alters synaptic terminal structure in hippocampus
Magariños, A. M., Verdugo, J. M. G., & McEwen, B. S. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.25.14002 · Cited by 543 · see citing works
Galea, L. A. M., McEwen, B. S., Tanapat, P., Deak, T., Spencer, R. L., & Dhabhar, F. S. (1997) · Neuroscience · doi:10.1016/s0306-4522(97)00233-9 · Cited by 540 · see citing works
Mattson, M. P., Rychlik, B., Chu, C., & Christakost, S. (1991) · Neuron · doi:10.1016/0896-6273(91)90120-o · Cited by 524 · see citing works
Bodnoff, S., Humphreys, A., Lehman, J., Diamond, D. M., Rose, G., & Meaney, M. (1995) · Journal of Neuroscience · doi:10.1523/jneurosci.15-01-00061.1995 · Cited by 522 · see citing works
Organizational effects of early gonadal secretions on sexual differentiation in spatial memory.
Williams, C. L., Barnett, A. M., & Meck, W. H. (1990) · Behavioral Neuroscience · doi:10.1037//0735-7044.104.1.84 · Cited by 486 · see citing works
Mizoguchi, K., Yuzurihara, M., Ishige, A., Sasaki, H., Chui, D.-H., & Tabira, T. (2000) · The Journal of Neuroscience · doi:10.1523/jneurosci.20-04-01568.2000 · Cited by 481 · see citing works
The organizational effects of gonadal steroids on sexually dimorphic spatial ability
Williams, C. L., & Meck, W. H. (1991) · Psychoneuroendocrinology · doi:10.1016/0306-4530(91)90076-6 · Cited by 445 · see citing works
Luine, V. N., Richards, S. T., Wu, V., & Beck, K. D. (1998) · Hormones and Behavior · doi:10.1006/hbeh.1998.1473 · Cited by 445 · see citing works
Self-citationAtkinson, H. C., & Waddell, B. J. (1997) · Endocrinology · doi:10.1210/endo.138.9.5395 · Cited by 438 · see citing works
The influence of ovarian steroids on hypothalamic-pituitary-adrenal regulation in the female rat
Carey, M. P., Deterd, C. H., de Koning, J., Helmerhorst, F., & de Kloet, E. R. (1995) · Journal of Endocrinology · doi:10.1677/joe.0.1440311 · Cited by 385 · see citing works
The relationship between stress induced cortisol levels and memory differs between men and women
Wolf, O. T., Schommer, N. C., Hellhammer, D. H., McEwen, B. S., & Kirschbaum, C. (2001) · Psychoneuroendocrinology · doi:10.1016/s0306-4530(01)00025-7 · Cited by 362 · see citing works
Wood, G. E., & Shors, T. J. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.7.4066 · Cited by 359 · see citing works
Phenytoin prevents stress‐ and corticosterone‐induced atrophy of CA3 pyramidal neurons
Watanabe, Y., Gould, E., Cameron, H. A., Daniels, D. C., & McEwen, B. S. (1992) · Hippocampus · doi:10.1002/hipo.450020410 · Cited by 350 · see citing works
Restraint stress reversibly enhances spatial memory performance
Luine, V. N., Martinez, C., Villegas, M., Magariños, A. M., & McEwen, B. S. (1996) · Physiology & Behavior · doi:10.1016/0031-9384(95)02016-0 · Cited by 249 · see citing works
Self-citationChronic restraint stress enhances radial arm maze performance in female rats
Bowman, R. E., Zrull, M. C., & Luine, V. N. (2001) · Brain Research · doi:10.1016/s0006-8993(01)02474-x · Cited by 247 · see citing works
Self-citationBowman, R. E., Ferguson, D., & Luine, V. N. (2002) · Neuroscience · doi:10.1016/s0306-4522(02)00156-2 · Cited by 224 · see citing works
Self-citationEffects of estradiol on radial arm maze performance of young and aged rats
Luine, V. N., & Rodríguez, M. S. (1994) · Behavioral and Neural Biology · doi:10.1016/s0163-1047(05)80021-4 · Cited by 222 · see citing works
Self-citationSex differences in behavioral and neurochemical profiles after chronic stress
Beck, K. D., & Luine, V. N. (2002) · Physiology & Behavior · doi:10.1016/s0031-9384(02)00670-4 · Cited by 211 · see citing works
Self-citationAnisman, H., Hayley, S. P., Kelly, O. P., Borowski, T. B., & Merali, Z. (2001) · Behavioral Neuroscience · doi:10.1037/0735-7044.115.2.443 · Cited by 206 · see citing works
Kudielka, B. M., Hellhammer, J., Hellhammer, D. H., Wolf, O. T., Pirke, K., Váradi, E., Pilz, J., & Kirschbaum, C. (1998) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.83.5.4758 · Cited by 196 · see citing works
Patchev, V. K., Hayashi, S., Orikasa, C., & Almeida, O. F. X. (1995) · The FASEB Journal · doi:10.1096/fasebj.9.5.7896013 · Cited by 193 · see citing works
Luine, V. N., Spencer, R. L., & McEwen, B. S. (1993) · Brain Research · doi:10.1016/0006-8993(93)90193-q · Cited by 168 · see citing works
Self-citationThe hippocampal formation: Morphological changes induced by thyroid, gonadal and adrenal hormones
Gould, E. A., Woolley, C. S., & McEwen, B. S. (1991) · Psychoneuroendocrinology · doi:10.1016/0306-4530(91)90071-z · Cited by 157 · see citing works
Adaptation of female rats to stress: shift to male pattern by inhibition of corticosterone synthesis
Haleem, D. J., Kennett, G. A., & Curzon, G. (1988) · Brain Research · doi:10.1016/0006-8993(88)90476-3 · Cited by 157 · see citing works
Stages of estrous mediate the stress-induced impairment of associative learning in the female rat
Shors, T. J., Lewczyk, C., Pacynski, M., Mathew, P. R., & Pickett, J. (1998) · Neuroreport · doi:10.1097/00001756-199802160-00012 · Cited by 149 · see citing works
Chronic Corticosterone Impairs Memory Performance in the Barnes Maze
McLay, R. N., Freeman, S. M., & Zadina, J. E. (1998) · Physiology & Behavior · doi:10.1016/s0031-9384(97)00529-5 · Cited by 146 · see citing works
Gender, Sex Steroids, Corticotropin-Releasing Factor, Nitric Oxide, and the HPA Response to Stress
RIVIER, C. L. (1999) · Pharmacology Biochemistry and Behavior · doi:10.1016/s0091-3057(99)00148-3 · Cited by 137 · see citing works
Kudielka, B. M., Schmidt-Reinwald, A. K., Hellhammer, D. H., & Kirschbaum, C. (1999) · Neuroendocrinology · doi:10.1159/000054504 · Cited by 135 · cited 1× · see citing works
“Other support for gonadal hormone influences on the HPA axis comes from a study of post menopausal women, with or without two weeks of estradiol treatment, and young pre-menopausal women (Kudielka et al., 1999).”
BackgroundBeck, K. D., & Luine, V. N. (1999) · Brain Research · doi:10.1016/s0006-8993(99)01380-3 · Cited by 127 · see citing works
Self-citationSpontaneous recognition of object configurations in rats: effects of fornix lesions
Ennaceur, A., & Aggleton, J. P. (1994) · Experimental Brain Research · doi:10.1007/bf00227281 · Cited by 121 · see citing works
Servatius, R. J., & Shors, T. J. (1994) · Behavioral Neuroscience · doi:10.1037/0735-7044.108.6.1101 · Cited by 98 · see citing works
Lewis, C., McEwen, B. S., & Frankfurt, M. (1995) · Developmental Brain Research · doi:10.1016/0165-3806(95)00052-f · Cited by 90 · see citing works
Altemus, M. M., Redwine, L. S., Leong, Y.-M., MD, D. L. M., Ph.D, T. Y., Detera-Wadleigh, S. D., & Ph.D, R. Y. (1997) · Neuropsychopharmacology · doi:10.1016/s0893-133x(97)00039-0 · Cited by 84 · see citing works
McIntyre, D., Kent, P., Hayley, S. P., Merali, Z., & Anisman, H. (1999) · Brain Research · doi:10.1016/s0006-8993(99)01771-0 · Cited by 79 · see citing works
Steroid Hormone Influences on Spatial Memory
Luine, V. N. (1994) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1994.tb55793.x · Cited by 64 · see citing works
Self-citationFerrini, M. G., Piroli, G. G., Frontera, M., Falbo, A., Lima, A. E., & Nicola, A. F. D. (1999) · Neuroendocrinology · doi:10.1159/000054411 · Cited by 49 · see citing works
McCormick, C. M., & Mahoney, E. (1999) · Hormones and Behavior · doi:10.1006/hbeh.1998.1500 · Cited by 46 · see citing works
Patchev, V., Hayashi, S., Orikasa, C., & Almeida, O. F. X. (1999) · Stress · doi:10.3109/10253899909001111 · Cited by 34 · see citing works
Sex Differences in Chronic Stress Effects on Cognitive Function and Brain Neurochemistry
Luine, V. N., Beck, K. D., Bowman, R. E., et al. (2001) · CRC Press eBooks · doi:10.1201/9781420041194.ch23 · Cited by 12 · see citing works
Self-citationEstrogens differentially enhance spatial and non-spatial memory
Frankfurt, M., Mohan, G., Gordon, M. N., et al. (2001) · The Society for Neuroscience Abstracts · Cited by 1 · see citing works
Flagged first, then by citations
Research works printed but not linked: 2
- Kneavel, M., Chrisakos, S., Ferguson, D. and Luine, V. (2000). "Effect of chronic stress in calbindin-D28 knockout and wild-type mice: spatial and non-spatial memory tasks". Neuroendocrine Workshop on Estrogen, Growth Factors and Neuroplasticity. Am. Neuroendo. Soc., Toronto.
- Nelson, R.J. (2000) An Introduction to Behavioral Endocrinology Chapter 11, Stress, (Sinauer Associates, Sunderland, MA), pp 557 -592.
Cited by
Sorted by citations
Russo, S. J., Murrough, J. W., Han, M.-H., Charney, D. S., & Nestler, E. J. (2012) · Nature Neuroscience · doi:10.1038/nn.3234 · Cited by 1,206 · see citing works
A meta-analytic review of the effects of acute cortisol administration on human memory
Het, S., Ramlow, G., & Wolf, O. T. (2005) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2005.03.005 · Cited by 414 · see citing works
Chronic stress: Implications for neuronal morphology, function and neurogenesis
Joëls, M., Karst, H., Krugers, H. J., & Lucassen, P. J. (2007) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2007.04.001 · Cited by 381 · see citing works
Sex differences in anxiety and emotional behavior
Donner, N. C., & Lowry, C. A. (2013) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-013-1271-7 · Cited by 379 · see citing works
Stress, cognitive impairment and cell adhesion molecules
Sandi, C. (2004) · Nature reviews. Neuroscience · doi:10.1038/nrn1555 · Cited by 374 · see citing works
Chronic stress effects on memory: sex differences in performance and monoaminergic activity
Bowman, R. E., Beck, K. D., & Luine, V. N. (2003) · Hormones and Behavior · doi:10.1016/s0018-506x(02)00022-3 · Cited by 290 · see citing works
Self-citationPopma, A., Vermeiren, R., Geluk, C. A. M. L., Rinne, T., van den Brink, W., Knol, D. L., Jansen, L. M. C., van Engeland, H., & Doreleijers, T. A. H. (2007) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.06.006 · Cited by 290 · see citing works
Viau, V., Bingham, B., Davis, J., Lee, P., & Wong, M. (2005) · Endocrinology · doi:10.1210/en.2004-0846 · Cited by 266 · see citing works
Chen, Y., Rex, C. S., Rice, C. J., Dubé, C. M., Gall, C. M., Lynch, G., & Baram, T. Z. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1003825107 · Cited by 256 · see citing works
Schwabe, L., Dalm, S., Schächinger, H., & Oitzl, M. S. (2008) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2008.07.015 · Cited by 228 · see citing works
Stress effects on BDNF expression: Effects of age, sex, and form of stress
Bath, K. G., Schilit, A., & Lee, F. S. (2013) · Neuroscience · doi:10.1016/j.neuroscience.2013.01.074 · Cited by 197 · see citing works
Arousal and cortisol interact in modulating memory consolidation in healthy young men.
Kuhlmann, S., & Wolf, O. T. (2006) · Behavioral Neuroscience · doi:10.1037/0735-7044.120.1.217 · Cited by 194 · see citing works
Peripheral and central mechanisms of stress resilience
Pfau, M. L., & Russo, S. J. (2015) · Neurobiology of Stress · doi:10.1016/j.ynstr.2014.09.004 · Cited by 170 · see citing works
Stark, R., Wolf, O. T., Tabbert, K., Kagerer, S., Zimmermann, M., Kirsch, P., Schienle, A., & Vaitl, D. (2006) · NeuroImage · doi:10.1016/j.neuroimage.2006.05.046 · Cited by 167 · see citing works
Sex differences in hippocampal function
Koss, W. A., & Frick, K. M. (2017) · Journal of Neuroscience Research · doi:10.1002/jnr.23864 · Cited by 156 · see citing works
Bali, A., Randhawa, P. K., & Jaggi, A. S. (2015) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2014.12.018 · Cited by 133 · see citing works
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MILLER, M. M., & McEWEN, B. S. (2006) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1364.023 · Cited by 101 · see citing works
Murray-Close, D., Han, G., Cicchetti, D., Crick, N. R., & Rogosch, F. A. (2008) · Developmental Psychology · doi:10.1037/a0012564 · Cited by 97 · see citing works
Stress and memory retrieval in women: No strong impairing effect during the luteal phase.
Schoofs, D., & Wolf, O. T. (2009) · Behavioral Neuroscience · doi:10.1037/a0015625 · Cited by 68 · see citing works
Burgado, J., Harrell, C. S., Eacret, D., Reddy, R., Barnum, C. J., Tansey, M. G., Miller, A. H., Wang, H., & Neigh, G. N. (2014) · Behavioural Brain Research · doi:10.1016/j.bbr.2014.08.060 · Cited by 42 · see citing works
The molecular basis of depression: implications of sex-related differences in epigenetic regulation
Kawatake-Kuno, A., Murai, T., & Uchida, S. (2021) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2021.708004 · Cited by 23 · see citing works
- Authors
- Luine, V.
- Affiliations
- City University of New York (US)
- Corresponding author
- Luine, Victoria
- Venue
- Stress
- Publisher
- Informa UK Limited
- Published
- 2002-01
- Volume
- 5
- Issue
- 3
- Pages
- 205-216
- ISSN
- 1025-3890 (ISSN-L)
- 1607-8888
- OpenAlex
- W2016095773
- Cited by
- 250
- References
- 51
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 4 · 2023: 9 · 2022: 9 · 2021: 9 · 2020: 13 · 2019: 9 · 2018: 8 · 2017: 10 · 2016: 5 · 2015: 14 · 2014: 10 · 2013: 9 · 2012: 12
- FWCI
- 4.40
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Stress (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health
- National Institute of General Medical Sciences
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- sex differences, chronic stress, memory, hypothalamic-pituitary-adrenal axis, object recognition memory, spatial memory, restraint stress, monoamines, serotonin, norepinephrine, GABA, dopaminergic activity, hippocampal CA3, amygdala, frontal cortex, estradiol, estrogen replacement therapy, ovariectomy, cognitive function
- MeSH terms
- Animals, Chronic Disease, Female, Humans, Male, Memory, Memory Disorders, Sex Characteristics, Stress, Physiological, Rats
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