title: Time course of the effects of lipopolysaccharide on prepulse inhibition and brain nitrite content in mice.
abstract: The systemic administration of lipopolysaccharide (LPS) induces time-dependent behavioral alterations, which are related to sickness behavior and depression. The time-course effects of LPS on prepulse inhibition (PPI) remain unknown. Furthermore, the time-dependent effects of LPS on central nitrite content had not been investigated. Therefore, we studied alterations induced by single LPS (0.5mg/kg, i.p.) administration to mice on parameters, such as PPI, depressive- and anxiety-like behaviors, working memory, locomotor activity and motor coordination, 1.5 and 24h post-LPS administration. IL-1β and TNFα in the blood and brain as well as brain nitrite levels were evaluated in the prefrontal cortex (PFC), hippocampus (HC) and striatum (ST). An overall hypolocomotion was observed 1.5h post-LPS, along with depressive-like behaviors and deficits in working memory. Increments in IL-1β content in plasma and PFC, TNFα in plasma and decreases in nitrite levels in the ST and PFC were also verified. Twenty-four hours post-LPS treatment, depressive-like behaviors and working memory deficits persisted, while PPI levels significantly reduced along with increases in IL-1β content in the PFC and a decrease in nitrite levels in the HC, ST and PFC. Our data demonstrate that a delayed increase (i.e., 24h post-LPS) in PPI levels ensue, which may be useful behavioral parameter for LPS-induced depression. A decrease in nitrergic neurotransmission was associated with these behavioral findings.
authors.affiliation: Postgraduate Program in Medical Microbiology, Department of Pathology, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil.
authors.forename: Charllyany Sabino
authors.initials: CS
authors.lastname: Custódio
authors.forename: Bruna Stefânia Ferreira
authors.initials: BS
authors.lastname: Mello
authors.forename: Rafaela Carneiro
authors.initials: RC
authors.lastname: Cordeiro
authors.forename: Fernanda Yvelize Ramos
authors.initials: FY
authors.lastname: de Araújo
authors.forename: João Henrique
authors.initials: JH
authors.lastname: Chaves
authors.forename: Silvânia Maria Mendes
authors.initials: SM
authors.lastname: Vasconcelos
authors.forename: Hélio Vitoriano
authors.initials: HV
authors.lastname: Nobre Júnior
authors.forename: Francisca Cléa Florenço
authors.initials: FC
authors.lastname: de Sousa
authors.forename: Mariana Lima
authors.initials: ML
authors.lastname: Vale
authors.forename: André Férrer
authors.initials: AF
authors.lastname: Carvalho
authors.forename: Danielle Silveira
authors.initials: DS
authors.lastname: Macêdo
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D007266:Inhibition, Psychological; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D013216:Reflex, Startle / Q000187:drug effects; D045442:Rotarod Performance Test; D013550:Swimming; D013997:Time Factors
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D009573:Nitrites; C482199:lipopolysaccharide, E coli O55-B5; D009569:Nitric Oxide