title: Oxytocin in the nucleus accumbens shell reverses CRFR2-evoked passive stress-coping after partner loss in monogamous male prairie voles.
abstract: Loss of a partner can have severe effects on mental health. Here we explore the neural mechanisms underlying increased passive stress-coping, indicative of depressive-like behavior, following the loss of the female partner in the monogamous male prairie vole. We demonstrate that corticotropin-releasing factor receptor 2 (CRFR2) in the nucleus accumbens shell mediates social loss-induced passive coping. Further, we show that partner loss compromises the oxytocin system through multiple mechanisms. Finally, we provide evidence for an interaction of the CRFR2 and oxytocin systems in mediating the emotional consequences of partner loss. Our results suggest that chronic activation of CRFR2 and suppression of striatal oxytocin signaling following partner loss result in an aversive emotional state that may share underlying mechanisms with bereavement. We propose that the suppression of oxytocin signaling is likely adaptive during short separations to encourage reunion with the partner and may have evolved to maintain long-term partnerships. Additionally, therapeutic strategies targeting these systems should be considered for treatment of social loss-mediated depression.
authors.affiliation: Department of Behavioural and Molecular Neurobiology, Institute of Zoology, University of Regensburg, 93053 Regensburg, Germany. Electronic address: oliver.bosch@ur.de.
authors.forename: Oliver J
authors.initials: OJ
authors.lastname: Bosch
authors.affiliation: Department of Cellular and Molecular Pharmacology, Department of Neuroscience, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064-3095, USA. Electronic address: joanna.dabrowska@rosalindfranklin.edu.
authors.forename: Joanna
authors.initials: J
authors.lastname: Dabrowska
authors.affiliation: Boston Children's Hospital, F.M. Kirby Neurobiology Center, Harvard Medical School, Boston, MA 02115, USA; Center for Translational Social Neuroscience, Department of Psychiatry and Behavioral Sciences, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30322, USA. Electronic address: Meera.Modi@gmail.com.
authors.forename: Meera E
authors.initials: ME
authors.lastname: Modi
authors.affiliation: Center for Translational Social Neuroscience, Department of Psychiatry and Behavioral Sciences, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30322, USA; Silvio O. Conte Center for Oxytocin and Social Cognition, Emory University, Atlanta, GA 30322, USA. Electronic address: zjohnso2@gmail.com.
authors.forename: Zachary V
authors.initials: ZV
authors.lastname: Johnson
authors.affiliation: Center for Translational Social Neuroscience, Department of Psychiatry and Behavioral Sciences, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30322, USA. Electronic address: akeebaugh@mriinterventions.com.
authors.forename: Alaine C
authors.initials: AC
authors.lastname: Keebaugh
authors.affiliation: Center for Translational Social Neuroscience, Department of Psychiatry and Behavioral Sciences, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30322, USA; Silvio O. Conte Center for Oxytocin and Social Cognition, Emory University, Atlanta, GA 30322, USA. Electronic address: cbarrett27@gmail.com.
authors.forename: Catherine E
authors.initials: CE
authors.lastname: Barrett
authors.affiliation: Center for Translational Social Neuroscience, Department of Psychiatry and Behavioral Sciences, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30322, USA; Center for Behavioral Neuroscience, Department of Psychology, Quinnipiac University, Hamden, CT 06518, USA. Electronic address: todd.h.ahern@gmail.com.
authors.forename: Todd H
authors.initials: TH
authors.lastname: Ahern
authors.affiliation: Center for Translational Social Neuroscience, Department of Psychiatry and Behavioral Sciences, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30322, USA; Silvio O. Conte Center for Oxytocin and Social Cognition, Emory University, Atlanta, GA 30322, USA. Electronic address: jguo4@emory.edu.
authors.forename: JiDong
authors.initials: J
authors.lastname: Guo
authors.affiliation: Schaller Research Group on Neuropeptides, German Cancer Research Center DKFZ, Cell Network Cluster of Excellence, University of Heidelberg, 69120 Heidelberg, Germany. Electronic address: v.grinevich@dkfz-heidelberg.de.
authors.forename: Valery
authors.initials: V
authors.lastname: Grinevich
authors.affiliation: Center for Translational Social Neuroscience, Department of Psychiatry and Behavioral Sciences, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30322, USA; Silvio O. Conte Center for Oxytocin and Social Cognition, Emory University, Atlanta, GA 30322, USA. Electronic address: drainni@emory.edu.
authors.forename: Donald G
authors.initials: DG
authors.lastname: Rainnie
authors.affiliation: Department of Behavioural and Molecular Neurobiology, Institute of Zoology, University of Regensburg, 93053 Regensburg, Germany.
authors.forename: Inga D
authors.initials: ID
authors.lastname: Neumann
authors.affiliation: Center for Translational Social Neuroscience, Department of Psychiatry and Behavioral Sciences, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30322, USA; Silvio O. Conte Center for Oxytocin and Social Cognition, Emory University, Atlanta, GA 30322, USA. Electronic address: lyoun03@emory.edu.
authors.forename: Larry J
authors.initials: LJ
authors.lastname: Young
mesh_terms: D000223:Adaptation, Psychological; D000818:Animals; D003411:Arvicolinae / Q000502:physiology*; D001345:Autoradiography; D001426:Bacterial Proteins; D003342:Corpus Striatum / Q000502:physiology; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage / Q000494:pharmacology; D003643:Death; D005260:Female; D057967:Infusions, Intraventricular; D008164:Luminescent Proteins; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008845:Microinjections; D009474:Neurons / Q000502:physiology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology*; D010121:Oxytocin / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology*; D010152:Pair Bond; D010286:Paraventricular Hypothalamic Nucleus / Q000502:physiology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000494:pharmacology; D011863:Radioimmunoassay; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D018045:Receptors, Oxytocin / Q000037:antagonists & inhibitors / Q000378:metabolism; D054832:Urocortins / Q000008:administration & dosage / Q000494:pharmacology; D014668:Vasotocin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D001426:Bacterial Proteins; C101531:CRF receptor type 2; D008164:Luminescent Proteins; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D034741:RNA, Small Interfering; D018019:Receptors, Corticotropin-Releasing Hormone; D018045:Receptors, Oxytocin; C426704:UCN3 protein, human; D054832:Urocortins; C528574:astressin-2B; C054562:yellow fluorescent protein, Bacteria; C076093:vasotocin, (beta-mercapto-beta,beta-cyclopentamethylenepropionic acid)-O-methyl-Tyr(2)-Thr(4)-Orn(8)-Tyr(9)-NH2; D010121:Oxytocin; D003346:Corticotropin-Releasing Hormone; D014668:Vasotocin
keywords: Corticotropin-releasing factor; Grieving; Partner separation; Passive stress-coping; Social loss; Stresscopin