title: Local oxytocin tempers anxiety by activating GABAA receptors in the hypothalamic paraventricular nucleus.
abstract: Oxytocin (Oxt) is released in various hypothalamic and extrahypothalamic brain areas in response to anxiogenic stimuli to regulate aspects of emotionality and stress coping. We examined the anxiolytic action of Oxt in the hypothalamic paraventricular nucleus (PVN) while appraising if Oxt recruits GABA neurons to inhibit the behavioral, hormonal, and neuronal response to stress in female prairie voles (Microtus ochrogaster). Voles received an injection of Oxt in the PVN either before or after an elevated platform stress to determine a time-course for the effects of Oxt on the hormonal stress response. Subsequently, we evaluated if ante-stress injections of Oxt affected anxiety-like behaviors as well as neuronal activity in the PVN, using real-time in-vivo retrodialysis and immunohistochemistry with c-Fos expression as a biomarker of neural activity. In addition, we exposed voles to Oxt and a GABAA receptor antagonist, concurrently, to evaluate the impact of pharmacological blockade of GABAA receptors on the anxiolytic effects of Oxt. Elevated platform stress amplified anxiety-like behaviors and hypothalamic-pituitary-adrenal (HPA) axis activity-catalyzing corticotrophin-releasing hormone (CRH) neuronal activity and augmenting corticosterone release in circulation. Ante-stress Oxt injections in the PVN blocked these stress effects while promoting PVN GABA activity and release. Post-stress Oxt treatments were ineffective. The anxiolytic effects of Oxt were hindered by concurrent pharmacological blockade of GABAA receptors. Together, our data demonstrate ante-stress treatments of Oxt in the PVN inhibit stress activation of the HPA axis through recruitment of GABAergic neurons, providing insights to the local circuitry and potential therapeutically-relevant mechanisms.
authors.affiliation: Department of Psychology and Program in Neuroscience, Florida State University, Tallahassee, FL 32306, USA.
authors.forename: Adam S
authors.initials: AS
authors.lastname: Smith
authors.affiliation: Department of Psychology and Program in Neuroscience, Florida State University, Tallahassee, FL 32306, USA.
authors.forename: Manal
authors.initials: M
authors.lastname: Tabbaa
authors.affiliation: Department of Psychology and Program in Neuroscience, Florida State University, Tallahassee, FL 32306, USA.
authors.forename: Kelly
authors.initials: K
authors.lastname: Lei
authors.affiliation: Department of Psychology and Program in Neuroscience, Florida State University, Tallahassee, FL 32306, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Eastham
authors.affiliation: Department of Psychology and Program in Neuroscience, Florida State University, Tallahassee, FL 32306, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Butler
authors.affiliation: Department of Psychology and Program in Neuroscience, Florida State University, Tallahassee, FL 32306, USA.
authors.forename: Latanya
authors.initials: L
authors.lastname: Linton
authors.affiliation: Department of Psychology and Program in Neuroscience, Florida State University, Tallahassee, FL 32306, USA.
authors.forename: Randy
authors.initials: R
authors.lastname: Altshuler
authors.affiliation: Department of Psychology and Program in Neuroscience, Florida State University, Tallahassee, FL 32306, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Psychology and Program in Neuroscience, Florida State University, Tallahassee, FL 32306, USA. Electronic address: zwang@psy.fsu.edu.
authors.forename: Zuoxin
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000818:Animals; D001007:Anxiety / Q000378:metabolism*; D003411:Arvicolinae; D001522:Behavior, Animal / Q000187:drug effects*; D003345:Corticosterone / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000187:drug effects / Q000378:metabolism; D005260:Female; D058785:GABA-A Receptor Agonists / Q000494:pharmacology*; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000378:metabolism; D007150:Immunohistochemistry; D017551:Microdialysis; D010120:Oxytocics / Q000494:pharmacology*; D010121:Oxytocin / Q000494:pharmacology*; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism*; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism*
chemical_list: D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D010120:Oxytocics; D016760:Proto-Oncogene Proteins c-fos; D011963:Receptors, GABA-A; D010121:Oxytocin; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone
keywords: Corticotrophinreleasing hormone; GABA; Hypothalamic-pituitary-adrenal axis; Oxytocin; Prairie vole; Retrodialysis