ArticleBiological psychiatry2017
Orexins Mediate Sex Differences in the Stress Response and in Cognitive Flexibility.
Article in Biological psychiatry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed, 136 citations in OpenAlex.
- Central hypocretin/orexin administration alleviates sleep/wake disturbances, anhedonia, and neuroinflammation in an animal model of seasonal affective disorder.Annals of medicine · 2026Article
- Functional Plasticity of Orexin/Hypocretin Neurons Balances Stress States.Biological psychiatry · 2026Review
- Sex-specific relationships between stress coping and avoidance behavior in adult mice.Biology of sex differences · 2026Article
- Orexinergic responses to environmental stressors in the zebrafish gut.Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology · 2026Article
- Social defeat stress responses in the stress alternative model are dependent on sex and anterior basolateral amygdala orexin 2 receptors.Biology of sex differences · 2026Article
- Sex differences in neuromodulatory subcortical systems and their implications for Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- A single glucocorticoid response element regulates sociability in a sex-specific manner.Molecular psychiatry · 2026Article
- Sex differences in interactions between the muscarinic-1 and orexin-1 receptors on cognitive flexibility in rats.Brain research · 2026Article
- Sex-Specific Effects of Hypocretin Receptor Signaling in Corticotropin-Releasing Factor Neurons on Alcohol Drinking, Anxiety, and Extended Amygdala Neuronal Excitability.Biological psychiatry global open science · 2026Article
- Sex-specific relationships between stress coping and avoidance behavior.bioRxiv : the preprint server for biology · 2026Article
- COAddiction biology · 2026Article
- Sleep Architecture Alterations Following High-Dose Steroid Pulse Therapy: A Pilot Study Using a Portable Electroencephalogram-Based Device.Neuropsychopharmacology reports · 2025Article
- Sleep deprivation engages the orexin/hypocretin system to regulate food reward seeking.The international journal of neuropsychopharmacology · 2025Article
- Orexin/Hypocretin Modulates Neuroinflammatory Response to LPS in a Sex and Brain-Region Specific Manner in Young Rats.Journal of neurochemistry · 2025Article
- A divergent astrocytic response to stress alters activity patterns via distinct mechanisms in male and female mice.Nature communications · 2025Article
- Exploring individual differences in fear extinction in male and female mice: insights from HPA axis, microbiota, and transcriptomics.Translational psychiatry · 2025Article
- Effects of Traumatic Brain Injury on the Orexin/Hypocretin System.Neurotrauma reports · 2025Review
- Fentanyl demand and seeking in female rats: Role of the orexin system and estrous cycle.Addiction neuroscience · 2024Article
- Hypocretin in the nucleus accumbens shell modulates social approach in female but not male California mice.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- A male-specific mechanism of meningeal nociceptor sensitization promoting migraine headache.Cephalalgia : an international journal of headache · 2024Article
14 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundWomen are twice as likely as men to experience stress-related psychiatric disorders. The biological basis of these sex differences is poorly understood. Orexins are altered in anxious and depressed patients. Using a rat model of repeated stress, we examined whether orexins contribute to sex differences in outcomes relevant to stress-related psychiatric diseases.
methodsBehavioral, neural, and endocrine habituation to repeated restraint stress and subsequent cognitive flexibility was examined in adult male and female rats. In parallel, orexin expression and activation were determined in both sexes, and chromatin immunoprecipitation was used to determine transcription factors acting at the orexin promoter. Designer receptors exclusively activated by designer drugs were used to inhibit orexin activation throughout repeated restraint to determine if the stress-related impairments in female rats could be reduced.
resultsFemale rats exhibited impaired habituation to repeated restraint with subsequent deficits in cognitive flexibility compared with male rats. Increased orexin expression and activation were observed in female rats compared with male rats. The higher expression of orexin messenger RNA in female rats was due to actions of glucocorticoid receptors on the orexin promoter, as determined by chromatin immunoprecipitation. Inhibition of orexins using designer receptors exclusively activated by designer drugs in female rats throughout repeated restraint abolished their heightened hypothalamic-pituitary-adrenal responsivity and reduced stress-induced cognitive impairments.
conclusionsOrexins mediate the impairments in adaptations to repeated stress and in subsequent cognitive flexibility exhibited by female rats and provide evidence for a broader role for orexins in mediating functions relevant to stress-related psychiatric diseases.
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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.