ArticleFrontiers in behavioral neuroscience2014
Exercise reverses the effects of early life stress on orexin cell reactivity in male but not female rats.
Article in Frontiers in behavioral neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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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
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 70 citations in OpenAlex.
- Pooled it
- Selective orexin receptor cross-over treatment increases resilience and expression of neuroplastic signaling genes.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 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
- Repeated Morphine Exposure Reversibly Impairs Spike Generation and Repetitive Firing in a Functionally Distinct Subpopulation of Orexin Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Contribution of hypothalamic orexin (hypocretin) circuits to pathologies of motivation.British journal of pharmacology · 2024Review
- Interaction between corticotropin-releasing factor, orexin, and dynorphin in the infralimbic cortex may mediate exacerbated alcohol-seeking behavior.Neurobiology of stress · 2024Article
- Pain-Insomnia-Depression Syndrome: Triangular Relationships, Pathobiological Correlations, Current Treatment Modalities, and Future Direction.Pain and therapy · 2024Review
- Prolonged stress alters the PC1/PC2 ratio in the rat lateral hypothalamus, implicating impaired orexin maturation.Iranian journal of basic medical sciences · 2024Article
- Characteristics of Seltorexant-Innovative Agent Targeting Orexin System for the Treatment of Depression and Anxiety.Molecules (Basel, Switzerland) · 2023Review
- Early Life Stress AffectsInternational journal of molecular sciences · 2022Review
- From Molecule to Behavior: Hypocretin/orexin Revisited From a Sex-dependent Perspective.Endocrine reviews · 2022Review
- Physiological Role of Orexinergic System for Health.International journal of environmental research and public health · 2022Review
- Insulin-like Growth Factor I Couples Metabolism with Circadian Activity through Hypothalamic Orexin Neurons.International journal of molecular sciences · 2022Article
- Orexin, serotonin, and energy balance.WIREs mechanisms of disease · 2022Review
- Hippocampal neurogenesis mediates sex-specific effects of social isolation and exercise on fear extinction in adolescence.Neurobiology of stress · 2021Article
- The orexin (hypocretin) neuropeptide system is a target for novel therapeutics to treat cocaine use disorder with alcohol coabuse.Neuropharmacology · 2021Review
- The Insomnia-Addiction Positive Feedback Loop: Role of the Orexin System.Frontiers of neurology and neuroscience · 2021Review
- Influences of Stress and Sex on the Paraventricular Thalamus: Implications for Motivated Behavior.Frontiers in behavioral neuroscience · 2021Article
- Orexin/hypocretin receptor modulation of anxiolytic and antidepressive responses during social stress and decision-making: Potential for therapy.Brain research · 2020Review
- The contribution of orexins to sex differences in the stress response.Brain research · 2020Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Early life stress (ELS) is a known antecedent for the development of mood disorders such as depression. Orexin neurons drive arousal and motivated behaviors in response to stress. We tested the hypothesis that ELS alters orexin system function and leads to an altered stress-induced behavioral phenotype in adulthood. We also investigated if voluntary exercise during adolescent development could reverse the ELS-induced changes. Male and female Wistar rats were subjected to maternal separation stress on postnatal days (PND) 2-14. A subset of animals was given access to running wheels in late adolescence (1hr/day, PND40-70). In adulthood, rats were exposed to restraint stress and then tested on the open field (OF) and elevated plus maze (EPM). Brains were processed for Fos-protein and orexin or tyrosine hydroxylase immunohistochemistry. Restraint stress stimulated Fos-protein expression in perifornical area orexin cells, the paraventricular hypothalamic nucleus, and paraventricular thalamic nuclei, but this neuronal response was dampened in male and female rats exposed to ELS. ELS also reduced exploration in the OF, without affecting EPM behavior. These neural and behavioral changes are consistent with a depressive-like phenotype. Adolescent exercise reversed the orexin and behavioral deficits in ELS males. Exercise was not protective in females, although this may be due to sex differences in running behavior. Our findings highlight the inherent plasticity of the orexin system-a trait that may lead to a state of pathological rewiring but could also be treated using non-pharmacological approaches. We also highlight a need to better understand the sex-specific changes in orexin circuits and stress-related pathology.
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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.