Depressive behavior in mice due to immune stimulation is accompanied by reduced neural activity in brain regions involved in positively motivated behavior.
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.
Stone
Eric A
EA
Department of Psychiatry, New York University School of Medicine, New York, New York 10016, USA. eric.stone@nyu.edu
Lehmann
Michael L
ML
Lin
Yan
Y
Quartermain
David
D
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
D000276:Adjuvants, Immunologic; D018759:Adrenergic Uptake Inhibitors; D008070:Lipopolysaccharides; D016760:Proto-Oncogene Proteins c-fos; D012110:Reserpine; D020928:Mitogen-Activated Protein Kinases