{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T04:26:17Z","timestamp":1784607977929,"version":"3.55.0"},"reference-count":48,"publisher":"Wiley","issue":"20","license":[{"start":{"date-parts":[[2014,9,15]],"date-time":"2014-09-15T00:00:00Z","timestamp":1410739200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"NIH","award":["DK-55530"],"award-info":[{"award-number":["DK-55530"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2014,10,15]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\"><jats:list-item><jats:p>The prototypical stress hormone, corticotropin releasing factor (CRF), and the prototypical anti\u2010stressor hormone, oxytocin (OXT), are known to modulate brainstem neurocircuits involved in visceral reflexes.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>We demonstrated recently that the brainstem neurocircuits through which OXT exerts its actions are modulated by vagal afferent fibres; however, it is unknown whether the OXT\u2010induced modulation of brainstem vagal neurocircuits is also regulated differentially by CRF.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>Here we elucidate the cellular mechanisms and the effects on gastric tone of OXT following exposure of vagal brainstem neurones to CRF and report that CRF induces short\u2010term plastic changes in OXT\u2010sensitive vagal neurocircuits.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>The results presented may represent a possible mechanism through which stress alters the central regulation of gastrointestinal functions and may reflect the vagal dysregulation occurring as a consequence of stress\u2010exacerbated functional dyspepsia.<\/jats:p><\/jats:list-item><\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Stress impairs gastric emptying, reduces stomach compliance and induces early satiety via vagal actions. We have shown recently that the ability of the anti\u2010stress neuropeptide oxytocin (OXT) to modulate vagal brainstem circuits undergoes short\u2010term plasticity via alterations in cAMP levels subsequent to vagal afferent fibre\u2010dependent activation of metabotropic glutamate receptors. The aim of the present study was to test the hypothesis that the OXT\u2010induced gastric response undergoes plastic changes in the presence of the prototypical stress hormone, corticotropin releasing factor (CRF). Whole cell patch clamp recordings showed that CRF increased inhibitory GABAergic synaptic transmission to identified corpus\u2010projecting dorsal motor nucleus of the vagus (DMV) neurones. In naive brainstem slices, OXT perfusion had no effect on inhibitory synaptic transmission; following exposure to CRF (and recovery from its actions), however, re\u2010application of OXT inhibited GABAergic transmission in the majority of neurones tested. This uncovering of the OXT response was antagonized by pretreatment with protein kinase\u00a0A or adenylate cyclase inhibitors, H89 and di\u2010deoxyadenosine, respectively, indicating a cAMP\u2010mediated mechanism. In naive animals, OXT microinjection in the dorsal vagal complex induced a NO\u2010mediated corpus relaxation. Following CRF pretreatment, however, microinjection of OXT attenuated or, at times reversed, the gastric relaxation which was insensitive to<jats:sc>l<\/jats:sc>\u2010NAME but was antagonized by pretreatment with a VIP antagonist. Immunohistochemical analyses of vagal motoneurones showed an increased number of oxytocin receptors present on GABAergic terminals of CRF\u2010treated or stressed<jats:italic>vs<\/jats:italic>. naive rats. These results indicate that CRF alters vagal inhibitory circuits that uncover the ability of OXT to modulate GABAergic currents and modifies the gastric corpus motility response to OXT.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jphysiol.2014.278192","type":"journal-article","created":{"date-parts":[[2014,8,16]],"date-time":"2014-08-16T00:21:15Z","timestamp":1408148475000},"page":"4591-4605","source":"Crossref","is-referenced-by-count":39,"title":["Plasticity in the brainstem vagal circuits controlling gastric motor function triggered by corticotropin releasing factor"],"prefix":"10.1113","volume":"592","author":[{"given":"Kirsteen N.","family":"Browning","sequence":"first","affiliation":[{"name":"Department of Neural and Behavioral Sciences Penn State University College of Medicine Hershey PA 17033 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"Babic","sequence":"additional","affiliation":[{"name":"Department of Neural and Behavioral Sciences Penn State University College of Medicine Hershey PA 17033 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Toti","sequence":"additional","affiliation":[{"name":"Department of Neural and Behavioral Sciences Penn State University College of Medicine Hershey PA 17033 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory M.","family":"Holmes","sequence":"additional","affiliation":[{"name":"Department of Neural and Behavioral Sciences Penn State University College of Medicine Hershey PA 17033 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F. 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