ArticlePloS one2010
Bi-directional effect of cholecystokinin receptor-2 overexpression on stress-triggered fear memory and anxiety in the mouse.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
9 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.
- Depressive symptoms at short-, medium-, and long-term follow-up after bariatric surgical procedures: A systematic review and meta-analysis.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2025Pooled it
- Potential gut-brain mechanisms behind adverse mental health outcomes of bariatric surgery.Nature reviews. Endocrinology · 2021Review
- Isolating the Role of Corticosterone in the Hypothalamic-Pituitary-Gonadal Transcriptomic Stress Response.Frontiers in endocrinology · 2021Article
- Validation of candidate anxiety disorder genes using a carbon dioxide challenge task.Biological psychology · 2015Article
- Functional synergy between cholecystokinin receptors CCKAR and CCKBR in mammalian brain development.PloS one · 2015Article
- Temporal association of elevated cholecystokininergic tone and adolescent trauma is critical for posttraumatic stress disorder-like behavior in adult mice.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Neuropeptide regulation of fear and anxiety: Implications of cholecystokinin, endogenous opioids, and neuropeptide Y.Physiology & behavior · 2012Review
- Chronic activation of corticotropin-releasing factor type 2 receptors reveals a key role for 5-HT1A receptor responsiveness in mediating behavioral and serotonergic responses to stressful challenge.Biological psychiatry · 2012Article
- Cholecystokinin knock-down in the basolateral amygdala has anxiolytic and antidepressant-like effects in mice.Neuroscience · 2012Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Fear, an emotional response of animals to environmental stress/threats, plays an important role in initiating and driving adaptive response, by which the homeostasis in the body is maintained. Overwhelming/uncontrollable fear, however, represents a core symptom of anxiety disorders, and may disturb the homeostasis. Because to recall or imagine certain cue(s) of stress/threats is a compulsory inducer for the expression of anxiety, it is generally believed that the pathogenesis of anxiety is associated with higher attention (acquisition) selectively to stress or mal-enhanced fear memory, despite that the actual relationship between fear memory and anxiety is not yet really established. In this study, inducible forebrain-specific cholecystokinin receptor-2 transgenic (IF-CCKR-2 tg) mice, different stress paradigms, batteries of behavioral tests, and biochemical assays were used to evaluate how different CCKergic activities drive fear behavior and hormonal reaction in response to stresses with different intensities. We found that in IF-CCKR-2 tg mice, contextual fear was impaired following 1 trial of footshock, while overall fear behavior was enhanced following 36 trials of footshock, compared to their littermate controls. In contrast to a standard Yerkes-Dodson (inverted-U shaped) stress-fear relationship in control mice, a linearized stress-fear curve was observed in CCKR-2 tg mice following gradient stresses. Moreover, compared to 1 trial, 36 trials of footshock in these transgenic mice enhanced anxiety-like behavior in other behavioral tests, impaired spatial and recognition memories, and prolonged the activation of adrenocorticotropic hormone (ACTH) and glucocorticoids (CORT) following new acute stress. Taken together, these results indicate that stress may trigger two distinctive neurobehavioral systems, depending on both of the intensity of stress and the CCKergic tone in the brain. A "threshold theory" for this two-behavior system has been suggested.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.