Endotoxin-induced reduction of social investigation by mice: interaction with amphetamine and anti-inflammatory drugs
Endotoxin-induced reduction of social investigation by mice: interaction with amphetamine and anti-inflammatory drugs
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DOI：
10.1007/s002130050353
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发表时间：
1997-08-01
影响因子：
3.4
通讯作者：
Winslow, JT
中科院分区：
文献类型：
--
作者：
Fishkin, RJ;Winslow, JT
先前的研究表明，内毒素诱导的大鼠疾病行为的某些方面可能是介导的白细胞介素-1刺激的事件，可以减弱皮质类固醇，环氧合酶抑制剂和白细胞介素-1受体拮抗剂。在目前的研究中，我们在成年雄性小鼠中复制并扩展了这些发现。使用相对低剂量的脂多糖（LPS; 15 μ g/kg，IP）在注射后2-3小时可靠地诱导幼年同种动物的社会调查减少50-60%。安非他明（2.0-4.0 mg/kg，IP，LPS前30 min）加重LPS诱导的研究减少。在LPS前1小时给予甲基强的松龙（10-30 mg/kg，IP）、吲哚美辛（3-30 mg/kg，IP）和布洛芬（1- 100 mg/kg，IP）在几个剂量下显著减少LPS诱导的疾病行为。地塞米松（0.1-10 mg/kg，IP）可部分拮抗呕吐。代表性黄酮类化合物rohitukine（0.01-100.0 mg/kg，IP）和白杨素（0.01-10 mg/kg，IP）也拮抗LPS诱导的社会调查缺陷。这些研究重复并扩展了先前在大鼠中的研究，以证明低剂量LPS的系统性作用、抗炎药物的拮抗作用和苯丙胺对LPS作用的增强作用。后者的研究结果是一致的调节作用，肾上腺素能激活白细胞介素-1释放刺激内毒素。
Previous studies indicate that some aspects of endotoxin-induced sickness behavior in rats may be mediated by interleukin-1 stimulated events and can be attenuated by corticosteroids, cyclooxygenase inhibitors and the interleukin-1-receptor antagonist. In the current studies, we replicate and extend these findings in adult male mice. A relatively low dose of lipopolysaccharide (LPS; 15 mu g/kg, IP) was used to reliably induce a 50-60% reduction in the social investigation of a juvenile conspecific at 2-3 h after injection. Amphetamine (2.0-4.0 mg/kg, IP, 30 min pre-LPS) exacerbated LPS-induced decreases in investigation. Administration of methylprednisolone (10-30 mg/kg, IP), indomethacin (3-30 mg/kg, IP), and ibuprofen (1-l00 mg/kg, IP) 1 h before LPS significantly reduced LPS-induced sickness behavior at several doses. Dexamethasone (0.1-10 mg/kg, IP) partially antagonized sickness. Representative flavonoids rohitukine (0.01-100.0 mg/kg, IP) and chrysin (0.01-10 mg/kg, IP) also antagonized LPS-induced deficits in social investigation. These studies replicate and extend previous studies in rat to demonstrate systematic effects of low doses of LPS, antagonism by anti-inflammatory drugs and enhancement of LPS effects by amphetamine. The latter findings are consistent with a modulatory role for adrenergic activation on interleukin-1 release stimulated by endotoxicity.