Endotoxin administration induced differential neurochemical activation of the rat brain stem nuclei

Lipopolisaccharide (LPS) is a potent activator of the immune system, but also activates the hypothalamic-pituitary-adrenocortical (HPA) axis and cerebral catecholamine systems. In the present study, the effect of peripheral LPS administration on catecholaminergic and serotonergic neurotransmission in discrete brainstem nuclei was examined. Two hours following systemic administration of LPS (1, 10, or 100 micrograms/kg) norepinephrine (NE) content in the locus coeruleous (LC) was significantly increased in a dose related manner. An increased dopamine (DA) turnover as reflected by the 3,4-dihydroxyphenylacetic (DOPAC) + Homovanillic acid (HVA)/DA ratio, [DO-PAC + HVA]/[DA], was also observed at the LC with the medium and high doses of LPS administered. Endotoxin caused the main effects in the nucleus of the tractus solitarii (NTS) in which (a) it was found NE content increased in a dose related fashion, (b) DA turnover index was elevated with 10 and 100 micrograms/kg LPS doses, and (c) levels of serotonin (5-HT) and its catabolite, 5-hydroxyindole-3-acetic acid (5-HIAA), were also significantly elevated following the injection of 10 or 100 micrograms/kg LPS. By contrast, a consistent lack of catecholaminergic and serotonergic responses to endotoxin treatment was observed at the level of midbrain Raphe nuclei (MRN). These results demonstrate that differential neurochemical changes may occur in the brainstem region with a rank order of activation by LPS that was NTS > LC > MRN, suggesting different neural substrate for central effects of peripheral immune activation.