Hrupka B J, Langhans W
Institute of Animal Sciences, Physiology and Animal Husbandry, Swiss Federal Institute of Technology, Schorenstrasse 16, Postfach, 8603, Schwerzenbach, Switzerland.
Pharmacol Biochem Behav. 2001 Feb;68(2):355-62. doi: 10.1016/s0091-3057(00)00463-9.
Rats consistently reduce their food intake following injection of bacterial lipopolysaccharides (LPS). Because LPS increases CNS serotonin (5-HT) turnover, and because increases in CNS 5-HT turnover are associated with a decrease in food intake, we conducted a series of studies to examine 5-HT's potential role in LPS-induced anorexia. Chronic CNS 5-HT depletion by cisterna magna (CM) administration of 5,7-dihydroxytryptamine (5,7-DHT) failed to attenuate LPS-induced (100 microg/kg, ip) anorexia. In subsequent experiments, LPS was injected at lights out (hour 0) and [8-hydroxy-2-(di-n-propylamino)tetraline (8-OH-DPAT)] or N-CBZ-[(8beta)-1,6-dimethylergolin-8-yl]methylamine (metergoline) was injected at hour 5 - the time when LPS-treated rats become anorectic. Food intake was measured during the subsequent 2 h. In LPS-treated rats, 8-OH-DPAT (62.5, 125, or 250 microg/kg, sc) injection increased food intake. In a 2 x 2 factorial arrangement of LPS and 8-OH-DPAT, 125 microg/kg 8-OH-DPAT increased food intake significantly more in LPS-treated rats than in non-LPS-treated rats (significant LPS x 8-OH-DPAT interaction). In LPS-treated rats, 1 and 5 mg/kg metergoline significantly enhanced food intake. However, in a 2 x 2 arrangement of LPS and metergoline, 1 mg/kg metergoline failed to increase food intake in LPS and non-LPS-treated rats in two separate trials. The ability of the 5-HT(1A) receptor agonist 8-OH-DPAT to attenuate LPS-induced anorexia in rats supports a role of 5-HT in LPS-induced anorexia.
注射细菌脂多糖（LPS）后，大鼠会持续减少食物摄入量。由于LPS会增加中枢神经系统（CNS）中血清素（5-HT）的周转率，且CNS中5-HT周转率的增加与食物摄入量的减少有关，因此我们进行了一系列研究，以检验5-HT在LPS诱导的厌食症中的潜在作用。通过脑池内（CM）注射5,7-二羟基色胺（5,7-DHT）使CNS中的5-HT长期耗竭，未能减轻LPS（100微克/千克，腹腔注射）诱导的厌食症。在随后的实验中，在熄灯时（第0小时）注射LPS，并在第5小时（LPS处理的大鼠开始出现厌食症的时间）注射[8-羟基-2-（二正丙基氨基）四氢萘（8-OH-DPAT）]或N-苄基碳酰基-[(8β)-1,6-二甲基麦角灵-8-基]甲胺（美替拉林）。在随后的2小时内测量食物摄入量。在LPS处理的大鼠中，注射8-OH-DPAT（62.5、125或250微克/千克，皮下注射）会增加食物摄入量。在LPS和8-OH-DPAT的2×2析因设计中，125微克/千克的8-OH-DPAT在LPS处理的大鼠中比在未用LPS处理的大鼠中更显著地增加了食物摄入量（LPS×8-OH-DPAT有显著交互作用）。在LPS处理的大鼠中，1毫克/千克和5毫克/千克的美替拉林显著增加了食物摄入量。然而，在LPS和美替拉林的2×2设计中，在两项单独的试验中，1毫克/千克的美替拉林未能增加LPS处理和未用LPS处理的大鼠的食物摄入量。5-HT（1A）受体激动剂8-OH-DPAT减轻大鼠LPS诱导的厌食症的能力支持了5-HT在LPS诱导的厌食症中的作用。
