Linthorst A C, Flachskamm C, Müller-Preuss P, Holsboer F, Reul J M
Max Planck Institute of Psychiatry, Department of Neuroendocrinology, Munich, Germany.
J Neurosci. 1995 Apr;15(4):2920-34. doi: 10.1523/JNEUROSCI.15-04-02920.1995.
In this study the effect of immune system stimulation and intracerebroventricular (i.c.v.) administration of interleukin-1 beta (IL-1 beta) on hippocampal serotonergic neurotransmission, behavioral activity, and the hypothalamic-pituitary-adrenocortical (HPA) axis is described. An in vivo microdialysis method was used to measure hippocampal extracellular concentrations of serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in conscious, freely moving rats. In addition, we established a method to continuously monitor free corticosterone levels in dialysates. Behavioral activity was scored by measuring the time during which rats were active (locomotion, grooming, eating, drinking). We found a significant, positive relationship between behavioral activity and hippocampal extracellular concentrations of 5-HT. Intraperitoneal (i.p.) administration of the bacterial endotoxin lipopolysaccharide (LPS; 30, 100, and 300 micrograms/kg body weight) produced an increase in the extracellular concentrations of 5-HT and 5-HIAA in the hippocampus, which was paralleled by a significant decline in behavioral activity and a marked increase in extracellular corticosterone levels. Thus, the close correlation between hippocampal extracellular 5-HT levels and behavioral activity observed in control rats was disrupted in the LPS-treated animals. The effects of i.p. LPS could be mimicked by i.c.v. application of recombinant human IL-1 beta (hIL-1 beta; 100 ng). i.c.v. pretreatment with the IL-1 receptor antagonist (IL-1ra; 10 micrograms) antagonized the hIL-1 beta-induced effects. IL-1ra showed no intrinsic effects. Furthermore, it was found that i.c.v. pretreatment with IL-1ra (10 micrograms) significantly attenuated the i.p. LPS-induced (100 micrograms/kg body weight) rise in hippocampal extracellular 5-HT levels.(ABSTRACT TRUNCATED AT 250 WORDS)
本研究描述了免疫系统刺激及脑室内（i.c.v.）注射白细胞介素-1β（IL-1β）对海马5-羟色胺能神经传递、行为活动及下丘脑-垂体-肾上腺皮质（HPA）轴的影响。采用体内微透析法测量清醒、自由活动大鼠海马细胞外5-羟色胺（5-HT）及其代谢产物5-羟吲哚乙酸（5-HIAA）的浓度。此外，我们建立了一种连续监测透析液中游离皮质酮水平的方法。通过测量大鼠活动（运动、梳理毛发、进食、饮水）的时间对行为活动进行评分。我们发现行为活动与海马细胞外5-HT浓度之间存在显著的正相关关系。腹腔内（i.p.）注射细菌内毒素脂多糖（LPS；30、100和300微克/千克体重）使海马中5-HT和5-HIAA的细胞外浓度升高，同时行为活动显著减少，细胞外皮质酮水平显著升高。因此，在LPS处理的动物中，对照大鼠中观察到的海马细胞外5-HT水平与行为活动之间的密切相关性被破坏。腹腔注射LPS的作用可通过脑室内应用重组人IL-1β（hIL-1β；100纳克）模拟。用IL-1受体拮抗剂（IL-1ra；10微克）进行脑室内预处理可拮抗hIL-1β诱导的作用。IL-1ra无内在作用。此外，发现用IL-1ra（10微克）进行脑室内预处理可显著减弱腹腔注射LPS（100微克/千克体重）诱导的海马细胞外5-HT水平升高。（摘要截短于250字）
