The administration of lipopolysaccharide (LPS) by different routes is used as an animal model for different types of infection or inflammation. LPS challenge is interpreted by the brain as a stressor causing changes in central neurotransmitter systems. The present study examines the effect of intracerebroventricular (I.C.V.) administration of LPS (5 mg/4 ml) or sterile saline (vehicle) on tyrosine hydroxylase (TH) activity in the median eminence (ME) and on expression of TH mRNA and TH protein in the arcuate nucleus of the hypothalamus. Animals were anaesthetised using ketamine (100 mg kg^-1)-xylacine (10 mg kg^-1) and humanely killed. Enzyme activity was measured at 3, 6 and 12 h after injection of saline or LPS, and TH expression was analysed at 6 and 12 h. Intracerebroventricular injection of vehicle induced a light but not significant reduction of the TH activity in the ME at 6 and 12 h in relation to intact animals. LPS injected in the third ventricle decreased significantly TH activity at 6 h (P < 0.04, ANOVA followed by Tukey’s post hoc test) but not at 3 and 12 h after injection as compared to sham operated animals. However, an in situ hybridization study to examine the mRNA TH expression in the arcuate nucleus showed that saline injection had no effect but LPS induced a reduction of 80.5 % in the number of TH+mRNA cells at 6 h and of 44 % at 12 h. In addition, immunohistochemical study for detection of TH expressing cells showed that LPS also reduced protein expression in the arcuate nucleus in a 89 % at 6 h and 44 % at 12 h. Saline injection had no effect on TH expression. Parallel sections were stained with Nissl staining and no differences in the total number of cells were found. These results show that the I.C.V. administration of LPS reduces transiently the dopaminergic activity in the mediobasal hypothalamus through a transcriptional action more than a direct action on the TH activity.

This work was supported by grant PI 2001/015 from Consejería de Educación, Gobierno Autonomo de Canarias.