Lipopolysaccharide-induced changes in monoamines in specific areas of the brain: blockade by interleukin-1 receptor antagonist.

The purpose of this study was to examine the specificity in the effects of lipopolysaccharide (LPS) on monoamine concentrations in different areas of the brain and the involvement of interleukin-1 (IL-1) in the LPS-induced effects. Adult male rats were injected i.p. with saline, 10 micrograms/kg body weight of LPS, or treated with 250 micrograms of IL-1 receptor antagonist (IL-1ra) 5 min before and 2 h after LPS. Several brain areas including the hippocampus (HI), caudate putamen (CP), the hypothalamic paraventricular nucleus (PVN), arcuate nucleus (AN), median eminence (ME) and the medial preoptic area (MPA) were microdissected and analyzed for neurotransmitter concentrations by HPLC-EC. LPS treatment produced marked increases in the concentrations of norepinephrine (NE), dopamine (DA), serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the PVN. In the AN, it increased DA concentrations and was without any effect on the MPA, ME, CP and HI. Treatment with IL-1ra in combination with LPS completely blocked the LPS-induced effects. It is concluded that LPS produces highly specific changes in monamine metabolism in the hypothalamus and that these effects are mediated at least in part by IL-1beta.