Linthorst A C, Flachskamm C, Holsboer F, Reul J M
Max Planck Institute of Psychiatry, Department of Neuroendocrinology, Munich, Germany.
Neuroscience. 1996 Jun;72(4):989-97. doi: 10.1016/0306-4522(95)00604-4.
An endotoxic challenge produces pronounced effects on the immune, endocrine and central nervous systems. However, information on the brain structures and neurotransmitter systems participating in the physiological responses after stimulation of the immune system is still scarce. Using an in vivo microdialysis method is conscious, freely moving rats, the present study describes the effects of an endotoxic challenge on hippocampal serotonergic and noradrenergic neurotransmission. Rats were equipped with a microdialysis probe in the hippocampus, which enables the stress-free measurement of extracellular concentrations of serotonin, noradrenaline and their respective metabolites 5-hydroxyindoleacetic acid and 3-methoxy-4-hydroxyphenylglycol. The behavioral activity was scored by measurement of the time during which rats were active (locomotion, grooming, eating, drinking). In the control rats a significant, positive relationship between the behavioral activity and hippocampal extracellular levels of serotonin, noradrenaline and 3-methoxy-4-hydroxyphenylglycol was found. Intraperitoneally injected bacterial endotoxin (lipopolysaccharide; 100 micrograms/kg body weight) increased extracellular concentrations of serotonin, 5-hydroxyindoleacetic acid, noradrenaline and 3-methoxy-4-hydroxyphenylglycol, whereas the behavioral activity was largely reduced, thus disrupting the correlation between behavioral activity and hippocampal levels of serotonin, noradrenaline and 3-methoxy-4-hydroxyphenylglycol. Intraperitoneal pretreatment of rats with the cyclo-oxygenase inhibitor indomethacin attenuated, but did not completely abolish, the endotoxin-induced increases in hippocampal extracellular levels of serotonin, noradrenaline and their metabolites. From these results it may be concluded that the hippocampal serotonin and noradrenaline neurotransmitter systems are part of the brain circuitry responsive to an endotoxic challenge. Moreover, arachidonic acid metabolites seem to represent important, but not the sole, mediators of the endotoxin-induced changes in hippocampal neurotransmission.
内毒素刺激对免疫、内分泌和中枢神经系统会产生显著影响。然而，关于参与免疫系统刺激后生理反应的脑结构和神经递质系统的信息仍然匮乏。本研究采用体内微透析方法，在清醒、自由活动的大鼠身上，描述了内毒素刺激对海马5-羟色胺能和去甲肾上腺素能神经传递的影响。给大鼠海马区植入微透析探针，可在无应激状态下测量细胞外5-羟色胺、去甲肾上腺素及其各自代谢产物5-羟吲哚乙酸和3-甲氧基-4-羟基苯乙二醇的浓度。通过测量大鼠活动（运动、梳理毛发、进食、饮水）的时间来记录行为活动。在对照大鼠中，发现行为活动与海马细胞外5-羟色胺、去甲肾上腺素和3-甲氧基-4-羟基苯乙二醇水平之间存在显著的正相关关系。腹腔注射细菌内毒素（脂多糖；100微克/千克体重）会增加细胞外5-羟色胺、5-羟吲哚乙酸、去甲肾上腺素和3-甲氧基-4-羟基苯乙二醇的浓度，而行为活动则大幅减少，从而破坏了行为活动与海马5-羟色胺、去甲肾上腺素和3-甲氧基-4-羟基苯乙二醇水平之间的相关性。用环氧化酶抑制剂吲哚美辛对大鼠进行腹腔预处理，可减弱但不能完全消除内毒素诱导的海马细胞外5-羟色胺、去甲肾上腺素及其代谢产物水平的升高。从这些结果可以得出结论，海马5-羟色胺和去甲肾上腺素神经递质系统是响应内毒素刺激的脑回路的一部分。此外，花生四烯酸代谢产物似乎是内毒素诱导的海马神经传递变化的重要但非唯一介质。
