title: Plasticity in the brainstem vagal circuits controlling gastric motor function triggered by corticotropin releasing factor.
abstract: Stress impairs gastric emptying, reduces stomach compliance and induces early satiety via vagal actions. We have shown recently that the ability of the anti-stress neuropeptide oxytocin (OXT) to modulate vagal brainstem circuits undergoes short-term plasticity via alterations in cAMP levels subsequent to vagal afferent fibre-dependent activation of metabotropic glutamate receptors. The aim of the present study was to test the hypothesis that the OXT-induced 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-projecting 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-application of OXT inhibited GABAergic transmission in the majority of neurones tested. This uncovering of the OXT response was antagonized by pretreatment with protein kinase A or adenylate cyclase inhibitors, H89 and di-deoxyadenosine, respectively, indicating a cAMP-mediated mechanism. In naive animals, OXT microinjection in the dorsal vagal complex induced a NO-mediated corpus relaxation. Following CRF pretreatment, however, microinjection of OXT attenuated or, at times reversed, the gastric relaxation which was insensitive to l-NAME 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-treated or stressed vs. 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.
authors.affiliation: Department of Neural and Behavioral Sciences, Penn State University College of Medicine, Hershey, PA, 17033, USA.
authors.forename: Kirsteen N
authors.initials: KN
authors.lastname: Browning
authors.affiliation: Department of Neural and Behavioral Sciences, Penn State University College of Medicine, Hershey, PA, 17033, USA.
authors.forename: Tanja
authors.initials: T
authors.lastname: Babic
authors.affiliation: Department of Neural and Behavioral Sciences, Penn State University College of Medicine, Hershey, PA, 17033, USA.
authors.forename: Luca
authors.initials: L
authors.lastname: Toti
authors.affiliation: Department of Neural and Behavioral Sciences, Penn State University College of Medicine, Hershey, PA, 17033, USA.
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Holmes
authors.affiliation: Department of Neural and Behavioral Sciences, Penn State University College of Medicine, Hershey, PA, 17033, USA.
authors.forename: F Holly
authors.initials: FH
authors.lastname: Coleman
authors.affiliation: Department of Neural and Behavioral Sciences, Penn State University College of Medicine, Hershey, PA, 17033, USA rtravagli@hmc.psu.edu.
authors.forename: R Alberto
authors.initials: RA
authors.lastname: Travagli
mesh_terms: D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D001933:Brain Stem / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D019706:Excitatory Postsynaptic Potentials; D059330:GABAergic Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D005746:Gastric Emptying; D053444:Inhibitory Postsynaptic Potentials; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D009473:Neuronal Plasticity; D009569:Nitric Oxide / Q000378:metabolism; D010121:Oxytocin / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018045:Receptors, Oxytocin / Q000235:genetics / Q000378:metabolism; D013270:Stomach / Q000294:innervation / Q000502:physiology; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology*
chemical_list: D000067956:Adenylyl Cyclase Inhibitors; D018045:Receptors, Oxytocin; D009569:Nitric Oxide; D010121:Oxytocin; D003346:Corticotropin-Releasing Hormone; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases