Anxiolytic effects and mechanisms of guvacoline in chronic unpredictable mild stress-induced mice
Objective To investigate the antianxiety activity of guvacoline in vivo and its potential mechanism induced by chronic and unpredictable mild stress.Methods Behavioral methods such as open field,light and dark box,and elevated cross maze were used to evaluate the effect of norarecoline on the behavior of anxious mice.The content of serum corticosterone,the levels of SOD,MDA,and CAT in serum and brain,and the levels of neurotransmitters and inflammatory factors in brain were detected by enzyme-linked immunoassay.Western blotting detected the expressions of NMDAR,CamkII,Kalirin,and Rac.Resluts Guvacoline can significantly reduce the total distance and average speed of the model mice in the open field,and increase the number of mouse activities.The penetration times and open chamber time of model mice in light and dark chamber experiment were significantly increased(P<0.05,0.01).Guvacoline could significantly reduce the number of times and the total distance of the closed arm in the elevated cross maze experiment(P<0.01).Serum Cort and MDA in 20 and 40 mg/kg guvacoline groups were significantly decreased(P<0.01,0.001),while SOD and CAT were significantly increased in all guvacoline dose groups(P<0.05,0.001).The MDA content in the brain tissue of mice in each dose group of guvacoline was significantly reduced(P<0.01 and 0.001),while the SOD and CAT contents were significantly increased(P<0.001).The contents of 5-HT,DA,NE,and GABA in brain tissue of mice in guvacoline each dose group were significantly increased(P<0.05,0.01,0.001).The content of TNF-α in guvacoline 40 mg/kg group was significantly decreased(P<0.05),and the contents of IL-6 and IL-1β in guvacoline dose groups were significantly decreased(P<0.05,0.001).The expressions of NMDARa,p-CAMkII/CamkII,Kalirin/β-actin,Rac/β-actin were significantly up-regulated in guvacoline 40 mg/kg group(P<0.001).Conclusion Guvacoline has significant anti-anxiety activity,and its mechanism is related to anti-oxidative stress injury,inhibition of neuroinflammatory response,regulation of neurotransmitter levels and NMDAR/CamkⅡ/Rac signaling pathway.
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