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

Abstract

Systemic administration of lipopolysaccharide (LPS) induces sickness behaviors, as well as alterations of hypothalamic–pituitary–adrenal functioning commonly associated with stressors. In the present investigation, it was demonstrated that systemic LPS treatment induced a sickness-like behavioral profile (reduced active behaviors, soporific effects, piloerection, ptosis), which appeared to be dependent upon the novelty of the environmental context in which animals were tested. As well, LPS induced anxiogenic-like responses, including decreased time spent in the illuminated portion of a light–dark box, reduced open-arm entries in a plus-maze test, and decreased contact with a novel stimulus object in an open-field situation. The behavioral changes 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 eminence plus arcuate nucleus, hippocampus, as well as NE turnover within the locus coeruleus and DA turnover within the nucleus accumbens. Although these neurochemical variations were reminiscent of those elicited by stressors, LPS was not particularly effective in modifying DA activity within the prefrontal cortex or NE within the amygdala, variations readily induced by stressors. Whether the LPS-induced anxiogenic-like responses were secondary to the illness engendered by the endotoxin remains to be determined. Nevertheless, it ought to be considered that bacterial endotoxin challenge, and the ensuing cytokine changes, may contribute to emotionality and perhaps even anxiety-related behavioral disturbances.