ENDOTOXIN ADMINISTRATION INDUCED DIFFERENTIAL NEUROCHEMICAL ACTIVATION OF THE RAT-BRAIN STEM NUCLEI

Lipopolisaccharide (LPS) is a potent activator of the immune system, b ut 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 hour s following systemic administration of LPS (1, 10, or 100 mu g/kg) nor epinephrine (NE) content in the locus coeruleous (LC) was significantl y increased in a dose related manner. An increased dopamine (DA) turno ver as reflected by the 3,4-dihydroxyphenylacetic (DOPAC) + Homovanill ic acid (HVA)/DA ratio, [DOPAC + HVA] / [DA], was also observed at the LC with the medium and high doses of LPS administered. Endotoxin caus ed the main effects in the nucleus of the tractus solitarii (NTS) in w hich (a) it was found NE content increased in a dose related fashion, (b) DA turnover index was elevated with 10 and 100 mu g/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 th e injection of 10 or 100 mu g/kg LPS. By contrast, a consistent lack o f catecholaminergic and serotonergic responses to endotoxin treatment was observed at the level of midbrain Raphe nuclei (MRN). These result s 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.