Individual differences in the effects of chronic stress on memory: behavioral and neurochemical correlates of resiliency
Abstract
Chronic stress has been shown to impair memory, however, the extent to which memory can be impaired is often variable across individuals. Predisposed differences in particular traits, such as anxiety, may reveal underlying neurobiological mechanisms that could be driving individual differences in sensitivity to stress and, thus, stress resiliency. Such pre-morbid characteristics may serve as early indicators of susceptibility to stress. Neuropeptide Y (NPY) and enkephalin (ENK) are neurochemical messengers of interest implicated in modulating anxiety and motivation circuitry; however, little is known about how these neuropeptides interact with stress resiliency and memory. In this experiment, adult male rats were appetitively trained to locate sugar rewards in a motivation-based spatial memory task before undergoing repeated immobilization stress and then being tested for memory retention. Anxiety-related behaviors, among other characteristics, were monitored longitudinally. Results indicated that stressed animals which showed little to no impairments in memory post-stress (i.e., the more stress-resilient individuals) exhibited lower anxiety levels prior to stress when compared to stressed animals that showed large deficits in memory (i.e., the more stress-susceptible individuals). Interestingly, all stressed animals, regardless of memory change, showed reduced body weight gain as well as thymic involution, suggesting that the effects of stress on metabolism and the immune system were dissociated from the effects of stress on higher cognition, and that stress resiliency seems to be domain-specific rather than a global characteristic within an individual. Neurochemical analyses revealed that NPY in the hypothalamus and amygdala and ENK in the nucleus accumbens were modulated differentially between stress-resilient and stress-susceptible individuals, with elevated expression of these neuropeptides fostering anxiolytic and pro-motivation function, thus driving cognitive resiliency in a domain-specific manner. Findings suggest that such neurochemical markers may be novel targets for pharmacological interventions that can serve to prevent or ameliorate the negative effects of stress on memory.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Chronic stress is associated with cognitive deficits, systemic inflammation, premature aging, immune system dysfunction, and a higher likelihood of metabolic disorders such as diabetes, cardiovascular disease, and IBD.
“Chronic stress is associated with various cognitive deficits, systemic inflammation, premature aging, immune system dysfunction, and a higher likelihood of suffering from metabolic disorders such as diabetes, cardiovascular disease, and IBD (490–492).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [490]
Cites
The rat brain in stereotaxic coordinates
Palkovits, M. (1983) · Neuropeptides · doi:10.1016/0143-4179(83)90049-5 · Cited by 28,959 · see citing works
The Rat Brain in Stereotaxic Coordinates
Paxinos, G., & Watson, C. (1983) · Elsevier eBooks · doi:10.1016/c2009-0-63235-9 · Cited by 28,585 · see citing works
The use of the elevated plus maze as an assay of anxiety-related behavior in rodents
Walf, A. A., & Frye, C. A. (2007) · Nature Protocols · doi:10.1038/nprot.2007.44 · Cited by 3,035 · see citing works
Stress revisited: a critical evaluation of the stress concept
Koolhaas, J. M., Bartolomucci, A., Buwalda, B., de Boer, S. F., Flügge, G., Korte, S. M., Meerlo, P., Murison, R., Olivier, B., Palanza, P., et al. (2011) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2011.02.003 · Cited by 1,626 · see citing works
Charney, D. S. (2004) · American Journal of Psychiatry · doi:10.1176/appi.ajp.161.2.195 · Cited by 1,605 · see citing works
Chronic mild stress-induced anhedonia: A realistic animal model of depression
Willner, P., Muscat, R., & Papp, M. (1992) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(05)80194-0 · Cited by 1,160 · cited 1× · see citing works
“RBWG and AS can be considered to be one aspect of dysphoric/depression-like behavior brought upon by stress (Willner et al., 1992) and the presence of habituation suggests that individuals are becoming less dysphoric over time.”
BackgroundThe Psychobiology of Depression and Resilience to Stress: Implications for Prevention and Treatment
Southwick, S. M., Vythilingam, M., & Charney, D. S. (2005) · Annual Review of Clinical Psychology · doi:10.1146/annurev.clinpsy.1.102803.143948 · Cited by 1,160 · see citing works
Learning under stress: how does it work?
Joëls, M., Pu, Z., Wiegert, O., Oitzl, M. S., & Krugers, H. J. (2006) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2006.02.002 · Cited by 947 · see citing works
Glucocorticoids, depression, and mood disorders: Structural remodeling in the brain
McEwen, B. S. (2005) · Metabolism · doi:10.1016/j.metabol.2005.01.008 · Cited by 687 · see citing works
Stress and Memory: Behavioral Effects and Neurobiological Mechanisms
Sandi, C., & Pinelo-Nava, M. T. (2007) · Neural Plasticity · doi:10.1155/2007/78970 · Cited by 611 · see citing works
Neuropeptide Y: A potent inducer of consummatory behavior in rats
Levine, A. S., & Morley, J. E. (1984) · Peptides · doi:10.1016/0196-9781(84)90165-7 · Cited by 564 · see citing works
Habituation to repeated stress: Get used to it
Grissom, N., & Bhatnagar, S. (2009) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2008.07.001 · Cited by 552 · see citing works
A Novel Mouse Model for Acute and Long-Lasting Consequences of Early Life Stress
Rice, C. J., Sandman, C. A., Lenjavi, M. R., & Baram, T. Z. (2008) · Endocrinology · doi:10.1210/en.2008-0633 · Cited by 521 · see citing works
Spatial memory and radial arm maze performance of rats
Olton, D. S., Collison, C., & Werz, M. A. (1977) · Learning and Motivation · doi:10.1016/0023-9690(77)90054-6 · Cited by 400 · see citing works
The role of endorphins in stress: Evidence and speculations
Amir, S., Brown, Z. W., & Amit, Z. (1980) · Neuroscience & Biobehavioral Reviews · doi:10.1016/0149-7634(80)90027-5 · Cited by 351 · see citing works
Social stress, therapeutics and drug abuse: Preclinical models of escalated and depressed intake
MICZEK, K., YAP, J., & COVINGTONIII, H. (2008) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2008.07.006 · Cited by 338 · see citing works
A critical review of chronic stress effects on spatial learning and memory
Conrad, C. D. (2009) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2009.11.003 · Cited by 335 · see citing works
Thorsell, A., Michalkiewicz, M., Dumont, Y., Quirion, R., Caberlotto, L., Rimondini, R., Mathé, A. A., & Heilig, M. A. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.220232997 · Cited by 315 · see citing works
Haglund, M., Nestadt, P. S., Cooper, N. S., Southwick, S. M., & Charney, D. S. (2007) · Development and Psychopathology · doi:10.1017/s0954579407000430 · Cited by 315 · see citing works
Criteria for rationally evaluating animal models of postraumatic stress disorder
Yehuda, R., & Antelman, S. M. (1993) · Biological Psychiatry · doi:10.1016/0006-3223(93)90001-t · Cited by 301 · see citing works
Cohen, H., Zohar, J., Gidron, Y., Matar, M. A., Belkind, D., Loewenthal, U., Kozlovsky, N., & Kaplan, Z. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.12.003 · Cited by 276 · see citing works
Learning under stress: The inverted-U-shape function revisitedPreprint
Salehi, B., Cordero, M. I., & Sandi, C. (2010) · Learning & Memory · doi:10.1101/lm.1914110 · Cited by 272 · see citing works
Brenes, J. C., Rodríguez‐Villagra, O. A., & Fornaguera, J. (2007) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2007.11.004 · Cited by 259 · see citing works
Yehuda, R., Brand, S. R., & Yang, R.-K. (2005) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.08.027 · Cited by 244 · see citing works
Social factors and individual vulnerability to chronic stress exposure
Bartolomucci, A., Palanza, P., Sacerdote, P., Panerai, A. E., Sgoifo, A., Dantzer, R., & Parmigiani, S. (2004) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2004.06.009 · Cited by 225 · see citing works
Social stress, immune functions and disease in rodents
Bartolomucci, A. (2007) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2007.02.001 · Cited by 209 · see citing works
Glucose-sensitive neurons in the rat arcuate nucleus contain neuropeptide Y
Muroya, S., Yada, T., Shioda, S., & Takigawa, M. (1999) · Neuroscience Letters · doi:10.1016/s0304-3940(99)00185-8 · Cited by 204 · see citing works
Pynoos, R. S., Ritzmann, R. F., Steinberg, A. M., Goenjian, A. K., & Prisecaru, I. (1996) · Biological Psychiatry · doi:10.1016/0006-3223(95)00088-7 · Cited by 200 · see citing works
Cohen, H., Matar, M. A., Buskila, D., Kaplan, Z., & Zohar, J. (2008) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.05.025 · Cited by 200 · see citing works
Vulnerability to Depression: From Brain Neuroplasticity to Identification of Biomarkers
Blugeot, A., Rivat, C., Bouvier, E., Molet, J., Mouchard, A., Zeau, B., Bernard, C., Benoliel, J., & Becker, C. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.1309-11.2011 · Cited by 187 · see citing works
Herrero, A. I., Sandi, C., & Venero, C. (2006) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2006.02.001 · Cited by 183 · see citing works
Neural Circuitry in the Regulation of Adrenal Corticosterone Rhythmicity
Engeland, W. C., & Arnhold, M. M. (2005) · Endocrine · doi:10.1385/endo:28:3:325 · Cited by 178 · see citing works
Behavioral and physiological characterization of male mice under chronic psychosocial stress
Bartolomucci, A., Pederzani, T., Sacerdote, P., Panerai, A. E., Parmigiani, S., & Palanza, P. (2003) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2003.08.003 · Cited by 177 · see citing works
Kleen, J. K., Sitomer, M. T., Killeen, P. R., & Conrad, C. D. (2006) · Behavioral Neuroscience · doi:10.1037/0735-7044.120.4.842 · Cited by 175 · see citing works
Thorsell, A., Carlsson, K., Ekman, R., & Heilig, M. A. (1999) · Neuroreport · doi:10.1097/00001756-199909290-00024 · Cited by 157 · see citing works
Behaviour in the elevated plus-maze predicts coping after subchronic mild stress in mice
Ducottet, C., & Belzung, C. (2004) · Physiology & Behavior · doi:10.1016/j.physbeh.2004.01.013 · Cited by 152 · see citing works
Sajdyk, T. J., Johnson, P. L., Leitermann, R. J., Fitz, S. D., Dietrich, A. D., Morin, M., Gehlert, D. R., Urban, J. H., & Shekhar, A. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.0659-07.2008 · Cited by 147 · see citing works
Self-citationLucas, L., Celen, Z., Tamashiro, K. L., Blanchard, R. J., Blanchard, D. C., Markham, C. M., Sakai, R. R., & McEwen, B. S. (2004) · Neuroscience · doi:10.1016/j.neuroscience.2003.12.009 · Cited by 145 · see citing works
Self-citationStress and the immune system in the etiology of anxiety and depression
Leonard, B. E., & Song, C. (1996) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(95)02158-2 · Cited by 124 · see citing works
Sainsbury, A., Rohner-Jeanrenaud, F., Cusin, I., Zakrzewska, K. E., Halban, P. A., Gaillard, R. C., & Jeanrenaud, B. (1997) · Diabetologia · doi:10.1007/s001250050820 · Cited by 115 · see citing works
Increased vulnerability to psychosocial stress in heterozygous serotonin transporter knockout mice
Bartolomucci, A., Carola, V., Pascucci, T., Puglisi‐Allegra, S., Cabib, S., Lesch, K., Parmigiani, S., Palanza, P., & Gross, C. T. (2010) · Disease Models & Mechanisms · doi:10.1242/dmm.004614 · Cited by 112 · see citing works
Brain neuropeptide Y and corticotropin-releasing hormone in mediating stress and anxiety
Thorsell, A. (2010) · Experimental biology and medicine · doi:10.1258/ebm.2010.009331 · Cited by 111 · see citing works
Repeated long separations from pups produce depression-like behavior in rat mothers
Boccia, M. L., Razzoli, M., Vadlamudi, S. P., Trumbull, W., Caleffie, C., & Pedersen, C. A. (2006) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2006.10.004 · Cited by 109 · see citing works
Glucocorticoid Involvement in Memory Formation in a Rat Model for Traumatic Memory
Cordero, M. I., Kruyt, N. D., Merino, J. J., & Sandi, C. (2002) · Stress · doi:10.1080/1025389029000124404 · Cited by 108 · see citing works
SHORT COMMUNICATION Selective enhancement of spatial learning under chronic psychosocial stress
Bartolomucci, A., de Biurrun, G., Czéh, B., van Kampen, M., & Fuchs, E. (2002) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2002.02043.x · Cited by 95 · see citing works
Touyarot, K., Venero, C., & Sandi, C. (2003) · Psychoneuroendocrinology · doi:10.1016/s0306-4530(03)00031-3 · Cited by 94 · see citing works
Central and peripheral mechanisms of the NPY system in the regulation of bone and adipose tissue
Shi, Y., & Baldock, P. A. J. (2011) · Bone · doi:10.1016/j.bone.2011.10.001 · Cited by 89 · see citing works
Sandi, C., Cordero, M. I., Ugolini, A., Varea, E., Caberlotto, L., & Large, C. H. (2008) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2008.06451.x · Cited by 85 · see citing works
Harris, R. B. S., Palmondon, J., Leshin, S., Flatt, W. P., & Richard, D. (2006) · Hormones and Behavior · doi:10.1016/j.yhbeh.2005.12.001 · Cited by 82 · see citing works
Larsen, P. J., Jessop, D. S., Chowdrey, H. S., Lightman, S. L., & Mikkelsen, J. D. (1994) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.1994.tb00566.x · Cited by 80 · see citing works
Ghiglieri, O., Gambarana, C., Scheggi, S., Tagliamonte, A., Willner, P., & Montis, M. G. D. (1997) · Behavioural Pharmacology · doi:10.1097/00008877-199711000-00018 · Cited by 78 · see citing works
Makino, Baker, B. I., Smith, & Gold (2000) · Journal of Neuroendocrinology · doi:10.1046/j.1365-2826.2000.00451.x · Cited by 77 · see citing works
Effects of immobilization stress on neurochemical markers in the motivational system of the male rat
Lucas, L., Wang, C.-J., McCall, T. J., & McEwen, B. S. (2007) · Brain Research · doi:10.1016/j.brainres.2007.04.063 · Cited by 71 · see citing works
Self-citationNeural mechanisms and computations underlying stress effects on learning and memory
Lukšys, G., & Sandi, C. (2011) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2011.03.003 · Cited by 64 · see citing works
Exponential decay of spatial memory of rats in a radial maze
Bolhuis, J. J., Bijlsma, S., & Ansmink, P. (1986) · Behavioral and Neural Biology · doi:10.1016/s0163-1047(86)90584-4 · Cited by 62 · see citing works
Antoniou, K. M., Papathanasiou, G., Papalexi, E., Hyphantis, T. N., Nomikos, G. G., Spyraki, C., & Papadopoulou‐Daifoti, Z. (2007) · Behavioural Brain Research · doi:10.1016/j.bbr.2007.10.010 · Cited by 50 · see citing works
Bonaventure, P., Nepomuceno, D. H., Mazur, C., Lord, B., Rudolph, D. A., Jablonowski, J. A., Carruthers, N. I., & Lovenberg, T. W. (2004) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.103.060459 · Cited by 44 · see citing works
Neurobiological and Endocrine Correlates of Individual Differences in Spatial Learning AbilityPreprint
Sandi, C., Cordero, M. I., Merino, J. J., et al. (2004) · Learning & Memory · doi:10.1101/lm.73904 · Cited by 40 · see citing works
Cordero, M. I., Kruyt, N. D., & Sandi, C. (2003) · Brain Research · doi:10.1016/s0006-8993(03)02352-7 · Cited by 37 · see citing works
Peripheral modulation of learning and memory: enkephalins as a model system
Schulteis, G., & Martinez, J. L. (1992) · Psychopharmacology · doi:10.1007/bf02245883 · Cited by 33 · see citing works
Central and peripheral effects of repeated stress and high NaCl diet on neuropeptide Y
Corder, R., Castagné, V., Rivet, J., Mormède, P., & Gaillard, R. C. (1992) · Physiology & Behavior · doi:10.1016/0031-9384(92)90259-5 · Cited by 33 · see citing works
Palkovits, M. (2008) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1410.062 · Cited by 28 · see citing works
Yohe, L. R., Suzuki, H., & Lucas, L. (2012) · Cognitive Affective & Behavioral Neuroscience · doi:10.3758/s13415-012-0095-9 · Cited by 22 · see citing works
Self-citationLucas, L., Dragisic, T., Duwaerts, C. C., Swiatkowski, M., & Suzuki, H. (2011) · Physiology & Behavior · doi:10.1016/j.physbeh.2011.06.017 · Cited by 21 · see citing works
Self-citationChronic passive exposure to aggression decreases D2 and 5-HT1B receptor densities
Suzuki, H., Han, S. D., & Lucas, L. (2010) · Physiology & Behavior · doi:10.1016/j.physbeh.2010.01.018 · Cited by 21 · see citing works
Self-citationCorticosterone binding globulin regulation and thymus changes after thermal injury in mice
D’Elia, M., Patenaude, J., Hamelin, C., et al. (2004) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00407.2004 · Cited by 18 · see citing works
Adding complexity to emotion-cognition interactions: the stressed individual
Sandi, C. (2008) · Frontiers in Neuroscience · doi:10.3389/neuro.01.042.2008 · Cited by 5 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Neuropeptide Y: a stressful review
Reichmann, F., & Holzer, P. (2016) · Neuropeptides · doi:10.1016/j.npep.2015.09.008 · Cited by 490 · see citing works
Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis
Rusch, J. A., Layden, B. T., & Dugas, L. R. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1130689 · Cited by 415 · see citing works
The molecular and cellular mechanisms of depression: a focus on reward circuitry
Fox, M. E., & Lobo, M. K. (2019) · Molecular Psychiatry · doi:10.1038/s41380-019-0415-3 · Cited by 232 · see citing works
Microbiota-gut-brain axis and cognitive function
Gareau, M. G. (2014) · Advances in Experimental Medicine and Biology · doi:10.1007/978-1-4939-0897-4_16 · Cited by 189 · see citing works
Kalapurakkel, S., A. Carpino, E., Lebel, A., & E. Simons, L. (2015) · Journal of Pediatric Psychology · doi:10.1093/jpepsy/jsu091 · Cited by 105 · see citing works
Repeated predictable stress causes resilience against colitis-induced behavioral changes in mice
Hassan, A. M., Jain, P., Reichmann, F., Mayerhofer, R., Farzi, A., Schuligoi, R., & Holzer, P. (2014) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2014.00386 · Cited by 59 · see citing works
Enkephalin downregulation in the nucleus accumbens underlies chronic stress-induced anhedonia
Poulin, J.-F., Laforest, S., & Drolet, G. (2014) · Stress · doi:10.3109/10253890.2013.850669 · Cited by 22 · see citing works
Levran, O., Peles, E., Randesi, M., Correa da Rosa, J., Shen, P.-H., Rotrosen, J., Adelson, M., & Kreek, M. J. (2018) · Pharmacogenomics · doi:10.2217/pgs-2017-0179 · Cited by 13 · see citing works
- Authors
- Sweis, B. M., Veverka, K. K., Dhillon, E. S., Urban, J. H., & Lucas, L. R.
- Affiliations
- University of Minnesota (US)
- Loyola University Chicago (US)
- Rosalind Franklin University of Medicine and Science (US)
- Corresponding author
- Lucas, L.R.
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 2013-08
- Volume
- 246
- Pages
- 142-159
- ISSN
- 0306-4522 (ISSN-L)
- OpenAlex
- W1981304687
- Cited by
- 39
- References
- 67
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 3 · 2022: 2 · 2021: 1 · 2020: 5 · 2019: 2 · 2018: 3 · 2017: 5 · 2015: 5 · 2014: 8 · 2013: 2
- FWCI
- 2.28
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of General Medical Sciences (T32GM008471)
- 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 › Neuropeptides and Animal Physiology
- Keywords
- chronic stress, stress resilience, memory impairment, individual differences, anxiety, neuropeptide Y, enkephalin, restraint stress, spatial memory, hypothalamus, amygdala, nucleus accumbens, thymic involution, weight gain, motivation, neurochemical markers, stress vulnerability
- MeSH terms
- Amygdala, Animals, Chronic Disease, Enkephalins, Hippocampus, Hypothalamus, Individuality, Male, Memory, Motivation, Neuropeptide Y, RNA, Messenger, Stress, Psychological, Rats, Sprague-Dawley, Rats, Resilience, Psychological
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
