The Effect of Cholecystokinin Octapeptide on Lipopolysaccharide-induced Sickness Behavior and Peripheral Cytokine Secretion

Abstract

Cytokines have been considered to be involved in the pathology of sickness behavior,but the role of peripheral cytokines in the pathology of sickness behavior is still elusive.Cholecystokinin octapeptide(CCK-8) has been proved to inhibit the lipopolysaccharide(LPS)-induced secretion of peripheral proinflammatory cytokines in rats.Aim:To investigate the role of peripheral cytokines in the pathology of sickness behavior.Methods:The experiment included two parts.In Experiment 1,forty-six rats were randomly divided into 4 groups:control,LPS,CCK-40+LPS and CCK-40,each group comprised twelve rats except ten rats for the control group,and in Experiment 2 forty-eight rats were randomly divided into six groups:control,LPS,CCK-20+LPS,CCK-40+LPS,CCK-80+LPS,CCK-120+LPS,each group comprised eight rats.The CCK groups were injected with different dosages of CCK-8 solution(20μg/kg,40μg/kg,80μg/kg and 120μg/kg doses respectively,i.p.) half an hour before the injection of LPS(200μg/kg,i.p.),and then 2 hours after the LPS injection,the sickness behavior was measured in behavioral experiments(including the sugar-water consumption test,open field test,and elevated plus maze test),and the cytokines in serum were analyzed by immunoassays.Results:LPS induced sickness behavior:LPS group consumed less sugar water and exhibited less activities in open field test and elevated plus maze test when compared with the controls;LPS also significantly increased cytokine production including IL-1β,IL-6 and TNF-α.However,the LPS-induced sickness behavior could not be attenuated by CCK-8,though CCK-8 significantly inhibited the LPS-induced proinflammatory cytokines of IL-1β,IL-6 and TNF-α compared to the LPS group.Conclusion:The inhibition of the secretion of peripheral proinflammatory cytokines can not antagonize the lipopolysaccharide-induced sickness behavior.The peripheral proinflammatory cytokines might be not directly responsible for the sickness behavior.The cytokines acting in brain may be more related to the sickness behavior,which needs further investigation.