The Study In The Correlation Between Anti-fluoxetine Mice’s Depressive-like Behaviors And The Level Of IL-1β In Brain

ObjectiveThe present study used 1 week’s fluoxetine hydrochloride(FLX) therapy after 8 weeks’ chronic unpredictable mild stress model(CUMS) to screening the anti-fluoxetine mice to mimic the clinic treatment-resistant depression(TRD) condition. And make statistic analysis between the depressive degree and interleukin-1 beta(IL-1β) of brain, find the relation between them.MethodThis study consisted of 2 parts which were all undertaken in mice:Part1: 50 male BABL/c mice were randomly divided into CONTROL, CUMS, CUMS + Treatment Group after 1 week’s adapting feeding. Mice in CONTROL Group were raised 9w ad libitum; CUMS group received 9w’s CUMS model intervention; CUMS + Treatment Group received 1w FLX(10mg/kg/day) after 8w’s CUMS intervention. At the end of the 8th week, the mice in CUMS + Treatment received weight test(BWT), sucrose preference test(SPT), open field test(OFT) and forced swim test(FST), and did those tests again at the end of 9th week. Screening the mice with depressive symptoms which had less improved as Fluoxetine-resistant mice(FRM) /Anti-depressant Resistant Mice(ATRM), on the other side, the mice which improved as the ordinary depressive mice(DM) based on the analysis of the difference of the SPT results(“Less Improved” was defined as the increase of the ratio in SPT < 10%; “Improved” was defined as the increase of the ratio in SPT > 20%). Make the respective evaluation of depressive behaviors of mice in CONTROL, CUMS, DM and ATRM group.Part2: At the endpoint of 9th week, the brain tissue of mice in CONTROL, CUMS, DM and ATRM group were extracted and the expression of IL-1β, interleukin-1 receptor antagonist(IL-1RA) and nuclear factor-κB(NF-κB) from different groups were evaluated by western blot(WB) and enzyme-linked immunosorbent assay(ELISA).ResultsPart1:(1) BWT: The mean body weight of CONTROL group was(24.56 ±5.45)g, CUMS was(19.03 ± 8.58)g, DM was(20.12 ± 9.17) g and ATRM was(18.56 ± 7.56) g. The body weight in CUMS, DM and ATRM group decreased at the 9th week. And the weight of mice in ATRM was significantly lower than that in CONTROL and DM group(P < 0.05).(2) SPT: the sucrose preference(SP) in CONTROL was 76%, in CUMS was 48%, in DM was 64%, in ATRM was 53% which was much lower than it in CONTROL and DM group(P < 0.05).(3) OFT and FST: there was no significant difference in horizontal movement distance(HMD) among the 4 groups(F = 0.327) in OFT; In FST, the immobility time(IT) in CONTROL was(208.25 ± 13.20) s, CUMS was(238.50 ± 13.38) s, DM was(156.00 ± 25.47) s, ATRM was(241.50 ± 36.55) s was longer than that in DM group(F = 13.573, P < 0.01).Part2:(1) There was no significant difference between each group in the expression of IL-1β(F = 0.643, P = 0.719) and NF-κB(F = 0.726,P = 0.851), but there was significant difference between each group in the expression of IL-1RA(F =32.459, P < 0.001).(2) There were significant differeces in the level of IL-1β among each groups(F = 62.14, P < 0.001). Post hoc further showed that the level of IL-1β in ATRM(164.90 ± 46.70 pg/mg) was higher than that in CONTROL(72.94 ± 1.44 pg/mg) and DM(93.09 ± 4.65 pg/mg), but with no significant difference to CUMS(177.978 ± 1.952 pg/mg).(3) Correlation between IL-1β and depressive behaviors: there was a positive correlation between the increase of IL-1β level and the immobility time in FST(r2 = 0.459, P = 0.006).Conclusion8 weeks’ CUMS model intervention could elicit depressive-like behaviors in mice and the short episode therapy of FLX could help to screening the ATRM from those mice. What’s more, the ATRM could mimic the characteristics of TRD in clinical patients after approving with behavior tests. The ATRM had higher level of IL-1β and IL-1RA expression, and there was positive correlation between the increased IL-1β level and IT in FST. In conclusion, the elevated level of IL-1β within CNS might play an important role in the development of TRD.