ArticleBiological psychiatry2014
Sex differences in corticotropin-releasing factor receptor-1 action within the dorsal raphe nucleus in stress responsivity.
Article in Biological psychiatry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 77 citations in OpenAlex.
- Corticotropin-Releasing Factor Receptor 1 Antagonism Is Ineffective for Women With Posttraumatic Stress Disorder.Biological psychiatry · 2017Trial
- Synaptic, cellular, and circuit mechanisms underlying sex differences in behaviors.Biology of sex differences · 2026Review
- A unifying theory of brain signaling and its possible role in acquired chronic disease.Frontiers in neuroscience · 2026Article
- Targeting corticotropin-releasing hormone receptor type 1 (Crhr1) neurons: validating the specificity of a novel transgenic Crhr1-FlpO mouse.Brain structure & function · 2024Article
- Alterations in hippocampal cholinergic dynamics following CRF infusions into the medial septum of male and female rats.Neurochemistry international · 2024Article
- Role of estrogen in sex differences in memory, emotion and neuropsychiatric disorders.Molecular biology reports · 2024Review
- Antagonists of the stress and opioid systems restore the functional connectivity of the prefrontal cortex during alcohol withdrawal through divergent mechanisms.bioRxiv : the preprint server for biology · 2024Article
- Sex Differences in Stress Response: Classical Mechanisms and Beyond.Current neuropharmacology · 2024Article
- Immune mechanisms of depression in rheumatoid arthritis.Nature reviews. Rheumatology · 2023Review
- Corticotropin releasing factor neurons in the visual cortex mediate long-term changes in visual function induced by early adversity.Neurobiology of stress · 2022Article
- Obstetric risk in pregnancy interacts with hair cortisone levels to reduce gestational length.Frontiers in global women's health · 2022Article
- Sex-Related Predisposition to Post-Traumatic Stress Disorder Development-The Role of Neuropeptides.International journal of environmental research and public health · 2021Review
- Alterations in corticotropin-releasing factor receptor type 1 in the preoptic area and hypothalamus in mice during the postpartum period.Hormones and behavior · 2021Article
- Stress Adaptation and the Brainstem with Focus on Corticotropin-Releasing Hormone.International journal of molecular sciences · 2021Review
- Considering Sex as a Biological Variable in Basic and Clinical Studies: An Endocrine Society Scientific Statement.Endocrine reviews · 2021Article
- Prefrontal corticotropin-releasing factor neurons impair sustained attention via distal transmitter release.The European journal of neuroscience · 2021Article
- Acute Corticotropin-Releasing Factor Receptor Type 2 Agonism Results in Sustained Symptom Improvement in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.Frontiers in systems neuroscience · 2021Article
- CRF-5-HT interactions in the dorsal raphe nucleus and motivation for stress-induced opioid reinstatement.Psychopharmacology · 2021Article
- Sex differences in corticotropin releasing factor peptide regulation of inhibitory control and excitability in central amygdala corticotropin releasing factor receptor 1-neurons.Neuropharmacology · 2020Article
- Vulnerability to helpless behavior is regulated by the circadian clock component CRYPTOCHROME in the mouse nucleus accumbens.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundWomen are twice as likely as men to suffer from stress-related affective disorders. Corticotropin-releasing factor (CRF) is an important link between stress and mood, in part through its signaling in the serotonergic dorsal raphe (DR). Development of CRF receptor-1 (CRFr1) antagonists has been a focus of numerous clinical trials but has not yet been proven efficacious. We hypothesized that sex differences in CRFr1 modulation of DR circuits might be key determinants in predicting therapeutic responses and affective disorder vulnerability.
methodsMale and female mice received DR infusions of the CRFr1 antagonist, NBI 35965, or CRF and were evaluated for stress responsivity. Sex differences in indices of neural activation (cFos) and colocalization of CRFr1 throughout the DR were examined. Whole-cell patch-clamp electrophysiology assessed sex differences in serotonin neuron membrane characteristics and responsivity to CRF.
resultsMales showed robust behavioral and hypothalamic-pituitary-adrenal axis responses to DR infusion of NBI 35965 and CRF, whereas females were minimally responsive. Sex differences were also found for both CRF-induced DR cFos and CRFr1 co-localization throughout the DR. Electrophysiologically, female serotonergic neurons showed blunted membrane excitability and divergent inhibitory postsynaptic current responses to CRF application.
conclusionsThese studies demonstrate convincing sex differences in CRFr1 activity in the DR, where blunted female responses to NBI 35965 and CRF suggest unique stress modulation of the DR. These sex differences might underlie affective disorder vulnerability and differential sensitivity to pharmacologic treatments developed to target the CRF system, thereby contributing to a current lack of CRFr1 antagonist efficacy in clinical trials.
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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.