Dunn Adrian J, Swiergiel Artur H
Department of Pharmacology, Toxicology and Neuroscience, Louisiana State University Health Sciences Center, LSU Health Sciences Center, P.O. Box 33932, Shreveport, LA 71130-3932, USA.
Pharmacol Biochem Behav. 2005 Jul;81(3):688-93. doi: 10.1016/j.pbb.2005.04.019.
Male CD-1 mice were administered interleukin-1beta (IL-1beta) and bacterial endotoxin (lipopolysaccharide, LPS) and subsequently tested in the tail suspension test (TST), the Porsolt forced swim test (FST), and in the open field. IL-1beta (100, 300 and 1000 ng/mouse) injected intraperitoneally (i.p.) 90 min before the test induced a dose-dependent increase in the time spent immobile in the TST and the time spent floating in the FST. These responses were statistically significant only at the higher doses of IL-1beta (300 and 1000 ng). Nevertheless, all three doses of IL-1beta significantly decreased line crossings and rears in the open field and depressed food intake and body weight. Very similar effects were induced by LPS. Doses of 1 and 5 mug i.p. increased immobility time in the TST and floating time in the FST, but the same doses strongly depressed locomotor activity and body weight. These results indicate that both IL-1beta and LPS can induce depression-like effects in the TST and the FST. However, the doses necessary to induce these changes reduced feeding and activity in an open field, so that the effects observed in the FST and TST could be attributed to a general reduction in locomotor activity. Thus the results obtained in these two animal tests commonly used to test antidepressant properties do not provide strong support for an IL-1 hypothesis of depression.
给雄性CD-1小鼠注射白细胞介素-1β(IL-1β)和细菌内毒素(脂多糖,LPS),随后在悬尾试验(TST)、波索尔特强迫游泳试验(FST)和旷场试验中进行测试。在试验前90分钟腹腔注射(i.p.)IL-1β(100、300和1000 ng/小鼠)可导致TST中不动时间和FST中漂浮时间呈剂量依赖性增加。这些反应仅在较高剂量的IL-1β(300和1000 ng)时具有统计学意义。然而,所有三种剂量的IL-1β均显著减少旷场试验中的穿格次数和直立次数,并降低食物摄入量和体重。LPS也诱导了非常相似的效应。腹腔注射1和5 μg的剂量增加了TST中的不动时间和FST中的漂浮时间,但相同剂量强烈抑制运动活动和体重。这些结果表明,IL-1β和LPS均可在TST和FST中诱导类似抑郁的效应。然而,诱导这些变化所需的剂量降低了旷场试验中的进食和活动,因此在FST和TST中观察到的效应可能归因于运动活动的普遍降低。因此,在这两种常用于测试抗抑郁特性的动物试验中获得的结果并不能为抑郁症的IL-1假说提供有力支持。