title: Depressive behavior in mice due to immune stimulation is accompanied by reduced neural activity in brain regions involved in positively motivated behavior.
abstract: BACKGROUND
  Immune stimulation inhibits positively motivated behavior and induces depressive illness. To help clarify the mechanism of these effects, neural activity in response to a positive stimulus was examined in brain regions associated with positively motivated activity defined on the basis of prior behavioral studies of central alpha1-adrenoceptor action.
  
  
  METHODS
  Mice pretreated with either lipopolysaccharide or, for comparison, reserpine were exposed to a motivating stimulus (fresh cage) and subsequently assayed for fos expression and mitogen-activated protein kinase (MAPK) phosphorylation, two measures associated with alpha1-adrenoceptor-dependent neural activity, in several positive-activity-related (motor, piriform, cingulate cortex, nucleus accumbens, locus coeruleus) and stress-related brain regions (paraventricular hypothalamus, bed nucleus stria terminalis).
  
  
  RESULTS
  Both lipopolysaccharide and reserpine pretreatment abolished fresh cage-induced fos expression and MAPK activation in the positive activity-related brain regions but enhanced these measures in the stress-related areas.
  
  
  CONCLUSIONS
  The results support the hypothesis that immune activation reduces alpha1-adrenoceptor-related signaling and neural activity in brain regions associated with positive activity while it increases these functions in stress-associated areas. It is suggested that neural activities of these two types of brain regions are mutually antagonistic and that a reciprocal shift toward the stress regions is a factor in the loss of positively motivated behaviors in sickness behavior and depressive illness.
authors.affiliation: Department of Psychiatry, New York University School of Medicine, New York, New York 10016, USA. eric.stone@nyu.edu
authors.forename: Eric A
authors.initials: EA
authors.lastname: Stone
authors.forename: Michael L
authors.initials: ML
authors.lastname: Lehmann
authors.forename: Yan
authors.initials: Y
authors.lastname: Lin
authors.forename: David
authors.initials: D
authors.lastname: Quartermain
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000502:physiology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003863:Depression / Q000139:chemically induced* / Q000523:psychology*; D005106:Exploratory Behavior / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009042:Motivation; D009474:Neurons / Q000187:drug effects*; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D012110:Reserpine / Q000494:pharmacology
chemical_list: D000276:Adjuvants, Immunologic; D018759:Adrenergic Uptake Inhibitors; D008070:Lipopolysaccharides; D016760:Proto-Oncogene Proteins c-fos; D012110:Reserpine; D020928:Mitogen-Activated Protein Kinases