Behavioral and neurochemical consequences of lipopolysaccharide in mice: anxiogenic-like effects

Systemic administration of lipopolysaccharide (LPS) induces sickness behavi ors, as well as alterations of hypothalamic-pituitary-adrenal functioning c ommonly associated with stressors. in the present investigation, it was dem onstrated that systemic LPS treatment induced a sickness-like behavioral pr ofile (reduced active behaviors, soporific effects, piloerection, ptosis), which appeared to be dependent upon the novelty of the environmental contex t in which animals were tested. As well, LPS induced anxiogenic-like respon ses, including decreased time spent in the illuminated portion of a light-d ark box, reduced open-arm entries in a plus-maze test, and decreased contac t with a novel stimulus object in an open-field situation. The behavioral c hanges were accompanied by increased plasma ACTH and corticosterone levels. As well, LPS induced increased turnover of norepinephrine (NE), dopamine ( DA) and serotonin (5-HT) in the paraventricular nucleus (PVN), median emine nce plus arcuate nucleus, hippocampus, as well as NE turnover within the lo cus coeruleus and DA turnover within the nucleus accumbens. Although these neurochemical variations were reminiscent of those elicited by stressors, L PS was not particularly effective in modifying DA activity within the prefr ontal cortex or NE within the amygdala, variations readily induced by stres sors. Whether the LPS-induced anxiogenic-like responses were secondary to t he illness engendered by the endotoxin remains to be determined. Neverthele ss, it ought to be considered that bacterial endotoxin challenge, and the e nsuing cytokine changes, may contribute to emotionality and perhaps even an xiety-related behavioral disturbances. (C) 1999 Elsevier Science B.V. All r ights reserved.