Pathogen-Host Defense in the Evolution of Depression: Insights into Epidemiology, Genetics, Bioregional Differences and Female Preponderance.
Neural and behavioral responses after peripheral immune challenge have been observed in numerous studies. The majority of these studies have utilized relatively high doses of lipopolysaccharide (LPS) as the immune stimulant. Little attention has been given to the effects of LPS dose ranges that simulate low grade-inflammation. The current studies were designed to characterize neural and behavioral responses following low-dose LPS stimulation. Results show burrowing and open field activity was significantly impaired following a single i.p. injection of 10, but not 1, μg/kg of LPS. In addition, following repeated 1 μg/kg LPS administration for 10 days, animals showed the progressive development of motor deficits over time. To correlate behavior with CNS activity, cFos activation was determined in the paraventricular nucleus, nucleus of the solitary tract, central amygdaloid nucleus, and ventrolateral medulla. Data revealed there was a dose-dependent activation in all brain areas examined, but only the PVN showed significant activation by low-dose LPS. Additionally, animals that received 1 μg/kg of LPS for 8 days had PVN cFos activation similar to animals that received a single 10 μg/kg LPS injection. These data demonstrate neural and behavior responses can be induced by low-grade inflammation and chronic exposure to sub-threshold levels of LPS can precipitate significantly heightened neural and behavioral responses.