Abstract: Objective: To investigate the circadian rhythmic alterations of plasma hormone and peptide induced by chronic unpredictable mild stress(CUMS).Methods: Sixty male SD rats were randomly divided into two groups, model group and control group(n=30). Rats in model group received CUMS procedure (restraint, rotation, cage tilt, wet sawdust, cold, crowding, food or water deprivation, clamp tail and reverse light/dark cycle). Rats were randomly exposed to two stressors every day for 3 weeks. Exploratory locomotor activity was assessed by open field test and anxiety-like behavior was measured by elevated plus-maze test, and lack of pleasure by sucrose preference test. Blood samples were collected at each of six time points zeitgeber time (ZT1, 5, 9, 13, 17 and 21), 5 rats were executed at each time point. Plasma concentrations of corticosterone(CORT), melatonin (MT) and vasoactive intestinal peptide (VIP) were detected by ELISA kits, and plasma concentration of adrenocorticotropic hormone (ACTH) was determined by radioimmunoassay. The circadian rhythm changes of serum CORT, MT, VIP and ACTH in each group were compared by using cosinor.Results: Compared with control group, locomotor activity, rearing, weight gain and sucrose consumption in model group were decreased significantly. The values of the percentage of open-arm time (OT) and open arm entries (OE) were obviously lower in the model group than those in the control group. The circadian rhythm of plasma ACTH and CORT showed an obvious disorder, including phase advance and decrease in amplitude, and markedly blunted circadian rhythm. There also showed a markedly blunted circadian rhythm and decreased levels of plasma MT. VIP still had 24-hour rhythm, but the amplitude was significantly lower, peak phase also delayed for six hours, and expression was significantly higher.Conclusion: CUMS induces these peptides and hormones desynchronized from suprachiasmatic nucleus(SCN), manifested as the disturbed circadian rhythms and the abnormal hormone secretion of these synchronizers.

Key words: chronic unpredictable mild stress, depressive-like behavior, neuroendocrine factor, circadian rhythms