脂多糖免疫激活对强迫游泳应激导致的抑郁样行为的影响

The Effect of Lipoposaccharide on Depressive-like Behavior Induced by Forced Swim Stress

应激导致抑郁样行为的同时导致免疫激活敏感化,但是免疫激活对应激导致的抑郁样行为的影响目前并不清楚。研究目的:利用脂多糖(Lipopolysaccharide,LPS)作为外周免疫激活启动剂,强迫游泳应激(forced swims tress)作为应激模式,考察免疫激活背景是否影响应激导致的抑郁样行为。方法:42只SD雄性大鼠随机分为四组:LS组(LPS+swim,n=12),LC组(LPS+空白,n=10),AS组(生理盐水+swim,n=10),AC组(生理盐水+空白,n=10)。在实验期第一天根据分组分别注射脂多糖(LPS,50μg/kg,腹腔注射)或生理盐水一次,LS组和AS组大鼠于注射后2小时进行第一次游泳应激,此后持续应激2周。分别在应激一次后,应激2周,应激结束后1周和应激结束后2周测定大鼠的糖精水偏爱、旷场行为和高架十字迷宫行为。结果显示:应激一次后,应激2周,应激后1周LS组大鼠与AC组相比较,糖精水偏爱分数,旷场中的水平活动显著下降;应激2周,AS组大鼠相对于AC组大鼠的糖精水偏爱分数以及旷场中的水平活动都显著下降,结论:慢性强迫性游泳应激导致抑郁样行为,应激前LPS免疫激活能够促使应激导致的抑郁样行为更容易出现,症状加剧,并持续较长的时间。

Stressful events engender multiple neurochemical and depressive-like behavior alteration as well as immune activation. Administration of lipoposaccharide （LPS）, which is known to activate immune functions and to induce the release of several cytokines both in the periphery and brain, also could engender depressive-like behavior alteration as same as stress. Many researchers paid attention to the effect of stress on immune activation. But few researches were related to the effect of activated–immune on the depressive-like behavior induced by stress. To further understand the role of immunity-activation induced cytokines in behavioral depression, the purpose of the present study was to investigate the effect of single administration of LPS prior to stress on depressive-like behavior induced by forced swim stress in rats. Forty-two rats were randomly divided into four groups： LS group （swim ＋ LPS, n=12）, LC group （LPS ＋ control, n=10）, AS group （saline ＋swim, n=10）, AC group （saline ＋ control, n=10）. On the first experiment day, according to groups, rates were injected intraperitoneally with LPS 50ug/kg and saline respectively. After 2h, LS and AS group rats were conducted forced swim stress for 14 days. On the 2end day, the 14th day, the 21st day and the 28th day, rats were tested with saccharin preference test, open field, elevated-plus maze. The results showed that saccharin preference percent, locomotion in open field, closed arms entries in elevated-plus maze in LS group were significant lower than that in AS group on the 2end day. On the 14th day, LS and AS group rats had fewer saccharin preference percent and locomotion than AC group rats. On the 21st day, LS group rats had significant decrease compared with AC group in saccharin preference percent and locomotion behavior. These results demonstrate that a series of easily onset and longer duration of depressive-like behavior was observed in LS group rats. It suggested that LPS-induced pro-inflammation cytokines may have synergistic and additive effects on depressive-like behavior induced by stress, there may be a cross-sensitization between them to cause depression.