ArticleMolecular psychiatry2023
Chronic oxytocin-driven alternative splicing of Crfr2α induces anxiety.
Article in Molecular psychiatry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 40 citations in OpenAlex.
- Androgens mediate sexual dimorphism in Pilarowski-Bjornsson syndrome.American journal of human genetics · 2026Article
- Hypothalamic oxytocin neurons produce pro-anxiety effects through glutamatergic projections to the lateral hypothalamus.Cell discovery · 2026Article
- Hypothalamic Oxytocin Neuronal Activation Induces Bipolar-Like Mood Changes in Mice in a Sex- and Dosage-Dependent Manner.Neuroscience bulletin · 2026Article
- Circuit logic of oxytocin and vasopressin complementary actions.Frontiers in neuroscience · 2026Review
- Prefrontal oxytocin receptor positive cells mediate stress-induced anxiety in tuberous sclerosis complex.Communications biology · 2025Article
- Oxytocin, Vasopressin and Stress: A Hormetic Perspective.Current issues in molecular biology · 2025Review
- PIEZO2 is the underlying mediator for precise magnetic stimulation of PVN to improve autism-like behavior in mice.Journal of nanobiotechnology · 2025Article
- OXTR-mediated signaling in astrocytes contributes to anxiolysis.Molecular psychiatry · 2025Article
- Functional involvement of septal miR-132 in extinction and oxytocin-mediated reversal of social fear.Molecular psychiatry · 2024Article
- CRF binding protein activity in the hypothalamic paraventricular nucleus is essential for stress adaptations and normal maternal behaviour in lactating rats.Neurobiology of stress · 2024Article
- Beyond fur color: differences in socio-emotional behavior and the oxytocin system between male BL6 and CD1 mice in adolescence and adulthood.Frontiers in neuroscience · 2024Article
- Therapeutic uses of oxytocin in stress-related neuropsychiatric disorders.Cell & bioscience · 2023Review
- Monitoring oxytocin signaling in the brain: More than a love story.Comprehensive psychoneuroendocrinology · 2023Review
- The role of the oxytocin system in the resilience of patients with breast cancer.Frontiers in oncology · 2023Review
- Transcriptome and chromatin alterations in social fear indicate association of MEG3 with successful extinction of fear.Molecular psychiatry · 2022Article
- Oxytocin as a potential pharmacological tool to combat obesity.Journal of neuroendocrinology · 2022Review
- Interactions between thePhilosophical transactions of the Royal Society of London. Series B, Biological sciences · 2022Review
- Altered PVN-to-CA2 hippocampal oxytocin pathway and reduced number of oxytocin-receptor expressing astrocytes in heart failure rats.Journal of neuroendocrinology · 2022Article
- Oxytocin and vasopressin: Signalling, behavioural modulation and potential therapeutic effects.British journal of pharmacology · 2022Review
- Effects of Intranasal Administration of Oxytocin and Vasopressin on Social Cognition and Potential Routes and Mechanisms of Action.Pharmaceutics · 2022Review
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Authors and funding
18 authors at 4 institutions in 1 country.
Funding
Abstract
The neuropeptide oxytocin (OXT) has generated considerable interest as potential treatment for psychiatric disorders, including anxiety and autism spectrum disorders. However, the behavioral and molecular consequences associated with chronic OXT treatment and chronic receptor (OXTR) activation have scarcely been studied, despite the potential therapeutic long-term use of intranasal OXT. Here, we reveal that chronic OXT treatment over two weeks increased anxiety-like behavior in rats, with higher sensitivity in females, contrasting the well-known anxiolytic effect of acute OXT. The increase in anxiety was transient and waned 5 days after the infusion has ended. The behavioral effects of chronic OXT were paralleled by activation of an intracellular signaling pathway, which ultimately led to alternative splicing of hypothalamic corticotropin-releasing factor receptor 2α (Crfr2α), an important modulator of anxiety. In detail, chronic OXT shifted the splicing ratio from the anxiolytic membrane-bound (mCRFR2α) form of CRFR2α towards the soluble CRFR2α (sCRFR2α) form. Experimental induction of alternative splicing mimicked the anxiogenic effects of chronic OXT, while sCRFR2α-knock down reduced anxiety-related behavior of male rats. Furthermore, chronic OXT treatment triggered the release of sCRFR2α into the cerebrospinal fluid with sCRFR2α levels positively correlating with anxiety-like behavior. In summary, we revealed that the shifted splicing ratio towards expression of the anxiogenic sCRFR2α underlies the adverse effects of chronic OXT treatment on anxiety.
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