title: Reversible inactivation of the dorsal vagal complex blocks lipopolysaccharide-induced social withdrawal and c-Fos expression in central autonomic nuclei.
abstract: Peripheral administration of lipopolysaccharide (LPS), a potent activator of the immune system, induces symptoms of behavioral depression, such as social withdrawal, concommitant with increases in c-Fos expression in central autonomic network nuclei. Previous studies implicated vagal visceral sensory nerves in transduction of immune-related signals relevant to for the induction of social withdrawal, a symptom of behavioral depression. Vagal sensory nerves terminate in the dorsal vagal complex (DVC) of the brainstem, a region that functions to integrate visceral signals and may also play a role in modulating arousal and affect. The objective of the current study was to determine whether the DVC contributes to immunosensory pathways driving symptoms of social withdrawal associated with LPS-induced behavioral depression, using a reversible lesion technique to temporarily inactivate the DVC. To assess the effects of DVC inactivation on LPS-induced social withdrawal and the subsequent changes in brain activation, we used behavioral assessment of social withdrawal, and analyzed c-Fos expression, a marker of neuronal activation, in the central nucleus of the amygdala (CEA), bed nucleus of the stria terminalis (BST), hypothalamic paraventricular nucleus (PVN), and ventromendial preoptic area (VMPO). Two hours following intraperitoneal LPS injection, there was a significant increase in c-Fos immunoreactivity in forebrain regions in animals treated with LPS. DVC inactivation completely blocked LPS-induced social withdrawal and dramatically reduced LPS-induced Fos expression in all four forebrain regions assessed. Collectively, these findings support the idea that the DVC acts as an immune-behavior interface between the peripheral stimuli and brain areas involved in modulating social behavior.
authors.affiliation: Department of Psychology and Neuroscience Graduate Program, University of Virginia, Charlottesville, VA 22904, USA.
authors.forename: Françoise A
authors.initials: FA
authors.lastname: Marvel
authors.forename: Chiao-Chi
authors.initials: CC
authors.lastname: Chen
authors.forename: Nadia
authors.initials: N
authors.lastname: Badr
authors.forename: Ron P A
authors.initials: RP
authors.lastname: Gaykema
authors.forename: Lisa E
authors.initials: LE
authors.lastname: Goehler
mesh_terms: D000210:Acute-Phase Reaction / Q000276:immunology / Q000378:metabolism; D000679:Amygdala / Q000378:metabolism; D000704:Analysis of Variance; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D031608:Area Postrema / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D017776:Autonomic Pathways / Q000276:immunology / Q000378:metabolism*; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D002045:Bupivacaine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008070:Lipopolysaccharides; D008297:Male; D008526:Medulla Oblongata / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D015213:Neuroimmunomodulation / Q000502:physiology*; D009475:Neurons, Afferent / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism; D011301:Preoptic Area / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012686:Septal Nuclei / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D012918:Social Alienation; D012919:Social Behavior; D017552:Solitary Nucleus / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D014630:Vagus Nerve / Q000166:cytology / Q000187:drug effects / Q000276:immunology*
chemical_list: D000779:Anesthetics, Local; D008070:Lipopolysaccharides; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D002045:Bupivacaine