Time course of the effects of lipopolysaccharide on prepulse inhibition and brain nitrite content in mice

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 (0.5 mg/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 24 h post-LPS administration. IL-1 β and TNF α 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 1.5 h post-LPS, along with depressive-like behaviors and de fi cits in working memory. Increments in IL-1 β content in plasma and PFC, TNF α in plasma and decreases in nitrite levels in the ST and PFC were also veri fi ed. Twenty-four hours post-LPS treatment, depressive-like behaviors and working memory de fi cits persisted, while PPI levels signi fi cantly reduced along with increases in IL-1 β 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., 24 h 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 fi ndings