ArticleBiological psychiatry2012
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.
Article in Biological psychiatry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 40 citations in OpenAlex.
- Acute and chronic stress differentially regulate pain via distinct ensembles in the paraventricular nucleus of hypothalamus.Molecular psychiatry · 2026Article
- Hunting for Genes Underlying Emotionality in the Laboratory Rat: Maps, Tools and Traps.Current neuropharmacology · 2023Review
- Serotonin deficiency induced after brain maturation rescues consequences of early life adversity.Scientific reports · 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
- Role of corticotropin-releasing factor in alcohol and nicotine addiction.Brain research · 2020Review
- Urocortin 3 signalling in the auditory brainstem aids recovery of hearing after reversible noise-induced threshold shift.The Journal of physiology · 2019Article
- A Major Role for the Lateral Habenula in Depressive Illness: Physiologic and Molecular Mechanisms.Frontiers in psychiatry · 2019Review
- The CRF Family of Neuropeptides and their Receptors - Mediators of the Central Stress Response.Current molecular pharmacology · 2018Review
- Overshadowed by the amygdala: the bed nucleus of the stria terminalis emerges as key to psychiatric disorders.Molecular psychiatry · 2016Review
- Allergic Diseases and Internalizing Behaviors in Early Childhood.Pediatrics · 2016Article
- Sex differences in corticotropin-releasing factor receptor-1 action within the dorsal raphe nucleus in stress responsivity.Biological psychiatry · 2014Article
- Fighting insomnia and battling lethargy: the yin and yang of palliative care.Current oncology reports · 2014Review
- Increased anxiety in corticotropin-releasing factor type 2 receptor-null mice requires recent acute stress exposure and is associated with dysregulated serotonergic activity in limbic brain areas.Biology of mood & anxiety disorders · 2014Article
- Corticotropin releasing hormone receptor 2 (CRHR-2) gene is associated with decreased risk and severity of posttraumatic stress disorder in women.Depression and anxiety · 2013Article
- Corticotropin-releasing factor-related peptides, serotonergic systems, and emotional behavior.Frontiers in neuroscience · 2013Review
- Desensitization of human CRF2(a) receptor signaling governed by agonist potency and βarrestin2 recruitment.Regulatory peptides · 2013Article
- 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
- Is it really a matter of simple dualism? Corticotropin-releasing factor receptors in body and mental health.Frontiers in endocrinology · 2013Article
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 3 countries.
Funding
Abstract
backgroundThe corticotropin-releasing factor type 2 receptor (CRFR2) is suggested to play an important role in aiding recovery from acute stress, but any chronic effects of CRFR2 activation are unknown. CRFR2 in the midbrain raphé nuclei modulate serotonergic activity of this key source of serotonin (5-HT) forebrain innervation.
methodsTransgenic mice overexpressing the highly specific CRFR2 ligand urocortin 3 (UCN3OE) were analyzed for stress-related behaviors and hypothalamic-pituitary-adrenal axis responses. Responses to 5-HT receptor agonist challenge were assessed by local cerebral glucose utilization, while 5-HT and 5-hydroxyindoleacetic acid content were quantified in limbic brain regions.
resultsMice overexpressing urocortin 3 exhibited increased stress-related behaviors under basal conditions and impaired retention of spatial memory compared with control mice. Following acute stress, unlike control mice, they exhibited no further increase in these stress-related behaviors and showed an attenuated adrenocorticotropic hormone response. 5-HT and 5-hydroxyindoleacetic acid content of limbic nuclei were differentially regulated by stress in UCN3OE mice as compared with control mice. Responses to 5-HT type 1A receptor challenge were significantly and specifically reduced in UCN3OE mice. The distribution pattern of local cerebral glucose utilization and 5-HT type 1A receptor messenger RNA expression levels suggested this effect was mediated in the raphé nuclei.
conclusionsChronic activation of CRFR2 promotes an anxiety-like state, yet with attenuated behavioral and hypothalamic-pituitary-adrenal axis responses to stress. This is reminiscent of stress-related atypical psychiatric syndromes such as posttraumatic stress disorder, chronic fatigue, and chronic pain states. This new understanding indicates CRFR2 antagonism as a potential novel therapeutic target for such disorders.
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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.