NMDA Receptors Mediate Lasting Increases in Anxiety-Like Behavior Produced by the Stress of Predator Exposure—Implications for Anxiety Associated with Posttraumatic Stress Disorder
Abstract
It has been proposed that NMDA-dependent long-term potentiation (LTP) of limbic system circuits controlling defensive behavior underlies stressor-induced lasting increases in anxiety-like behavior (ALB). Findings in cats given the stress-inducing beta-carboline, FG-7142, support this hypothesis. An animal model of lasting affective change following traumatic stress has recently been developed. In this model, lasting increases in anxiety-like behavior (ALB) assessed in the elevated plus maze are produced by a single 5-min exposure of a rat to a cat. Rats become more anxious in the plus maze for up to 3 weeks after the exposure. The present study demonstrates that blockade of NMDA receptors in rats with MK-801, AP7, or CPP, given 30 min prior to exposure to a cat, prevents the increase in ALB assessed 1 week later. MK-801 or AP7, given 30 min after exposure to a cat, do not prevent the increase in ALB seen 1 week later, however. MK-801, but not CPP or AP7, promotes approaches to cats during exposure. This "fearlessness" may reflect some anxiolytic action of MK-801. Approach to cats following injection of MK-801 was eliminated by prior injection of Prazosin. Prazosin did not interfere with the block of increases in ALB following cat exposure, however. These findings are consistent with the view that NMDA receptors are involved in initiation, but not maintenance of neural changes mediating lasting increases in anxiety following severe stress. The significance of these findings for PTSD are discussed.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Antipredator defensive behaviors in a visible burrow system
Blanchard, R. J., & Blanchard, D. C. (1989) · Journal of comparative psychology · doi:10.1037/0735-7036.103.1.70 · Cited by 663 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Diamond, D. M., Campbell, A. M., Park, C. R., Halonen, J., & Zoladz, P. R. (2007) · Neural Plasticity · doi:10.1155/2007/60803 · Cited by 762 · see citing works
“…work from this group (Schroeder and Shinnick-Gallagher [341]) and studies by Adamec et al. employing naturalistic (predator) stress (Adamec et al. [342]; Adamec et al. [288]; Rosen et al. [343]), all indicate that fear conditioning produces long-lasting increases in excitability in the amygdala.”
BackgroundStress duration modulates the spatiotemporal patterns of spine formation in the basolateral amygdala
Mitra, R., Jadhav, S., McEwen, B. S., Vyas, A., & Chattarji, S. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0504011102 · Cited by 663 · see citing works
Vyas, A., Pillai, A. G., & Chattarji, S. (2004) · Neuroscience · doi:10.1016/j.neuroscience.2004.07.013 · Cited by 445 · see citing works
Prolonged behavioral stress enhances synaptic connectivity in the basolateral amygdala
Vyas, A., Jadhav, S., & Chattarji, S. (2006) · Neuroscience · doi:10.1016/j.neuroscience.2006.08.003 · Cited by 299 · see citing works
Neighborhood matters: divergent patterns of stress-induced plasticity across the brain
Chattarji, S., Tomar, A., Suvrathan, A., Ghosh, S., & Rahman, M. M. (2015) · Nature Neuroscience · doi:10.1038/nn.4115 · Cited by 248 · see citing works
The Role of Life Events and HPA Axis in Anxiety Disorders: A Review
Faravelli, C., Lo Sauro, C., Lelli, L., Pietrini, F., Lazzeretti, L., Godini, L., Benni, L., Fioravanti, G., Alina Talamba, G., Castellini, G., et al. (2012) · Current Pharmaceutical Design · doi:10.2174/138161212803530907 · Cited by 208 · see citing works
McNaughton, N., Kocsis, B., & Hajós, M. (2007) · Behavioural Pharmacology · doi:10.1097/fbp.0b013e3282ee82e3 · Cited by 187 · see citing works
Adamec, R., Head, D., Blundell, J., Burton, P., & Berton, O. (2006) · Physiology & Behavior · doi:10.1016/j.physbeh.2006.03.005 · Cited by 145 · see citing works
Self-citationNeural circuit changes mediating lasting brain and behavioral response to predator stress
Adamec, R. E., Blundell, J., & Burton, P. (2005) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2005.05.007 · Cited by 121 · see citing works
Self-citationVouimba, R.-M., Muñoz, C., & Diamond, D. M. (2006) · Stress · doi:10.1080/10253890600610973 · Cited by 96 · see citing works
Neurons in the Amygdala with Response-Selectivity for Anxiety in Two Ethologically Based Tests
Wang, D. V., Wang, F., Liu, J., Zhang, L., Wang, Z., & Lin, L. (2011) · PLoS ONE · doi:10.1371/journal.pone.0018739 · Cited by 78 · see citing works
Schroeder, A., Notaras, M., Du, X., & Hill, R. A. (2018) · Brain Sciences · doi:10.3390/brainsci8070121 · Cited by 50 · see citing works
Adamec, R., Toth, M., Haller, J., Halasz, J., & Blundell, J. (2012) · Physiology & Behavior · doi:10.1016/j.physbeh.2011.09.016 · Cited by 37 · see citing works
Self-citationBhattacharya, S., Fontaine, A., MacCallum, P. E., Drover, J., & Blundell, J. (2019) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2019.00113 · Cited by 40 · see citing works
Impaired memory following predatory stress in mice is improved by fluoxetine
El Hage, W., Peronny, S., Griebel, G., & Belzung, C. (2004) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2003.09.028 · Cited by 28 · see citing works
Rodent anxiety and kindling of the central amygdala and nucleus basalis
Adamec, R., & Shallow, T. (2000) · Physiology & Behavior · doi:10.1016/s0031-9384(00)00250-x · Cited by 27 · see citing works
Self-citationPsychiatric aspects of infectious diseases
Mufaddel, A., Omer, A. A., & Salem, M. O. (2014) · Open Journal of Psychiatry · doi:10.4236/ojpsych.2014.43027 · Cited by 14 · see citing works
Selective Breeding for an Infantile Phenotype (Isolation Calling)
Brunelli, S. A., & Hofer, M. A. (2001) · Handbook of Behavioral Neurobiology · doi:10.1007/978-1-4615-1209-7_12 · Cited by 9 · see citing works
- Authors
- Adamec, R. E., Burton, P., Shallow, T., & Budgell, J.
- Affiliations
- Memorial University of Newfoundland (CA)
- Corresponding author
- Adamec, Robert E
- ORCID
- Burton, Paul
- Venue
- Physiology & Behavior
- Publisher
- Elsevier BV
- Published
- 1998-10
- Volume
- 65
- Issue
- 4-5
- Pages
- 723-737
- ISSN
- 0031-9384 (ISSN-L)
- OpenAlex
- W2035071372
- Cited by
- 171
- References
- 1
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 3 · 2023: 1 · 2022: 4 · 2021: 1 · 2020: 2 · 2019: 4 · 2018: 4 · 2017: 3 · 2016: 6 · 2015: 5 · 2014: 10 · 2013: 4 · 2012: 3
- FWCI
- 3.41
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Physiology & Behavior (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
- Keywords
- NMDA receptor, anxiety-like behavior, predator stress, post-traumatic stress disorder, long-term potentiation, MK-801, AP7, CPP, prazosin, alpha1-adrenoceptors, fearlessness, elevated plus maze, anxiolytic effects
- MeSH terms
- Amygdala, Animals, Anxiety, Behavior, Animal, Body Weight, Cats, Injections, Male, Predatory Behavior, Stress Disorders, Post-Traumatic, Stress, Psychological, Receptors, N-Methyl-D-Aspartate, Dizocilpine Maleate, Excitatory Amino Acid Antagonists, Rats
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
