ArticleMolecular psychiatry2013
An affective disorder in zebrafish with mutation of the glucocorticoid receptor.
Article in Molecular psychiatry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
100 citing papers in PubMed, 243 citations in OpenAlex.
- Mineralocorticoid and glucocorticoid receptor heterodimers mediate cortisol-induced behavioural changes via modulation of glutamatergic signalling.Molecular psychiatry · 2026Article
- TALE and Hox Transcription Factors Control Adult Behaviors in Zebrafish.bioRxiv : the preprint server for biology · 2026Article
- Crip2 preserves hematopoietic stem and progenitor cell production through inhibition of Notch signals.Development (Cambridge, England) · 2026Article
- Deciphering the gonadal cell atlas of Monopterus albus and cell fate during sex reversal based on single-cell RNA sequencing.Stem cell research & therapy · 2025Article
- Automated Behavioral Profiling Using Neural Networks Reveals Differences in Stress-Like Behavior Between Cave and Surface-Dwelling Astyanax mexicanus.Journal of experimental zoology. Part B, Molecular and developmental evolution · 2025Article
- Zebrafish as a Model Organism for Post-Traumatic Stress Disorder: Insights into Stress Mechanisms and Behavioral Assays.Biology · 2025Review
- Experimental PTSD Models in Zebrafish: A Systematic Review of Behavioral, Neurochemical, and Molecular Outcomes.Biology · 2025Review
- Early-life challenge enhances cortisol regulation in zebrafish larvae.Biology open · 2024Article
- Animal models in neuroscience with alternative approaches: Evolutionary, biomedical, and ethical perspectives.Animal models and experimental medicine · 2024Review
- Cortisol dynamics and GR-dependent feedback regulation in zebrafish larvae exposed to repeated stress.Biology open · 2024Article
- Elevated glucocorticoid alters the developmental dynamics of hypothalamic neurogenesis in zebrafish.Communications biology · 2024Article
- Key HPI axis receptors facilitate light adaptive behavior in larval zebrafish.Scientific reports · 2024Article
- Zebrafish-A Suitable Model for Rapid Translation of Effective Therapies for Pediatric Cancers.Cancers · 2024Review
- Glucocorticoid effects on the brain: from adaptive developmental plasticity to allostatic overload.The Journal of experimental biology · 2024Review
- Aging in zebrafish is associated with reduced locomotor activity and strain dependent changes in bottom dwelling and thigmotaxis.PloS one · 2024Article
- Decreased activity in zebrafish larvae exposed to glyphosate-based herbicides during development-potential mediation by glucocorticoid receptor.Frontiers in toxicology · 2024Article
- Multiple faces of stress in the zebrafish (Frontiers in physiology · 2024Article
- Glucocorticoid receptor regulates protein chaperone, circadian clock and affective disorder genes in the zebrafish brain.Disease models & mechanisms · 2023Article
- Breaking Through the Bottleneck: Krogh's Principle in Behavioral Neuroendocrinology and the Potential of Gene Editing.Integrative and comparative biology · 2023Review
- Flight for fish in drug discovery: a review of zebrafish-based screening of molecules.Biology letters · 2023Review
40 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 4 institutions in 5 countries.
Funding
Abstract
Upon binding of cortisol, the glucocorticoid receptor (GR) regulates the transcription of specific target genes, including those that encode the stress hormones corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone. Dysregulation of the stress axis is a hallmark of major depression in human patients. However, it is still unclear how glucocorticoid signaling is linked to affective disorders. We identified an adult-viable zebrafish mutant in which the negative feedback on the stress response is disrupted, due to abolition of all transcriptional activity of GR. As a consequence, cortisol is elevated, but unable to signal through GR. When placed into an unfamiliar aquarium ('novel tank'), mutant fish become immobile ('freeze'), show reduced exploratory behavior and do not habituate to this stressor upon repeated exposure. Addition of the antidepressant fluoxetine to the holding water and social interactions restore normal behavior, followed by a delayed correction of cortisol levels. Fluoxetine does not affect the overall transcription of CRH, the mineralocorticoid receptor (MR), the serotonin transporter (Serta) or GR itself. Fluoxetine, however, suppresses the stress-induced upregulation of MR and Serta in both wild-type fish and mutants. Our studies show a conserved, protective function of glucocorticoid signaling in the regulation of emotional behavior and reveal novel molecular aspects of how chronic stress impacts vertebrate brain physiology and behavior. Importantly, the zebrafish model opens up the possibility of high-throughput drug screens in search of new classes of antidepressants.
Indexed as
Identifiers
What OpenQuestion holds
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.