title: Inhibition of nitric oxide synthase accentuates endotoxin-induced sickness behavior in mice.
abstract: Sickness behavior appears to be the expression of a central motivational state that reorganizes an organism's priorities to cope with infectious pathogens. To evaluate the possible participation of nitric oxide (NO) in lipopolysaccharide-induced sickness behaviors, mice were submitted to the forced swim test (FST), open field test and dark-light box test. Food intake and corticosterone plasma levels were evaluated. Lipopolysaccharide (LPS, 100 μg/kg; i.p.) administration increased the time spent floating in the FST and decreased locomotor activity in the open field. Indeed, treatment with LPS decreased the total number of transitions between the dark and light compartments of the apparatus. In addition, LPS reduced food intake and increased corticosterone levels. Pretreatment with L-NAME (30 mg/kg; i.p.) or aminoguanidine (50mg/kg; i.p.) accentuated the behavioral changes induced by LPS in the FST, open field and light-dark box tests as well as induced an increment in hypophagia and in corticosterone levels. These findings confirm previous observations that have reported LPS-induced sickness behaviors. In addition, they provide evidence that the synthesis of NO modulates changes in depressive-like and exploratory behaviors in mice, which is supported by the fact that NO synthase inhibitors also attenuate LPS-induced behavioral changes. In addition, the present study suggests that NO may have a protective role, acting in an inhibitory feedback manner to limit LPS-induced sickness behavior.
authors.affiliation: Department of Physiological Science, Institute of Biomedical Sciences, Federal University of Alfenas-MG, Brazil.
authors.forename: Deidiane E
authors.initials: DE
authors.lastname: Ribeiro
authors.forename: Viviane M
authors.initials: VM
authors.lastname: Maiolini
authors.forename: Roseli
authors.initials: R
authors.lastname: Soncini
authors.forename: José
authors.initials: J
authors.lastname: Antunes-Rodrigues
authors.forename: Lucila L K
authors.initials: LL
authors.lastname: Elias
authors.forename: Fabiana C
authors.initials: FC
authors.lastname: Vilela
authors.forename: Alexandre
authors.initials: A
authors.lastname: Giusti-Paiva
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D003345:Corticosterone / Q000378:metabolism; D004357:Drug Synergism; D004435:Eating / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology; D006146:Guanidines / Q000494:pharmacology; D055809:Illness Behavior / Q000187:drug effects* / Q000502:physiology*; D008070:Lipopolysaccharides / Q000009:adverse effects*; D008297:Male; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010949:Plasma / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D006146:Guanidines; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; C004479:pimagedine; D019331:NG-Nitroarginine Methyl Ester; D003345:Corticosterone