?-asarone Improves Depress Ion-like Behaviors And Monoamine Neurotransmitters In Depressed Mice Induced By Chronic Unpredictable Mild Stress

Background.Depression is a common affective disorders disease,characterized by significant and lasting low mood,which results in tendency to commit suicide and aggressive behaviors in serious cases and imposes a major social and health burden on individuals,families and society.At present,prevalence rate of Depression has increased year by year worldwide,it is significant to strengthen the public awareness and education.Looking for effective antidepressant drugs from traditional Chinese medicine(TCM)has received an universal attentions from Medical workers.Acorus tatarinowii Schott,a traditional Chinese medicinal plant,has various pharmacological effects in central nervous system,so it can be good used in the treatmentson brain diseases.?-asarone is the main material basis for the pharmaceutical actions of Acorus tatarinowii Schott.Our previous studies have shown that ?-asarone can be delivered effectively across the blood-brain-barrier to the brain,?-asarone' and L-dopa co-administration can increase DA,DOPAC,HVA in the striatum and plasma of normal rats.monoamine neurotransmitters play important roles in the pathogenesis of depression.Whether ?-asarone have the role of improving depressive symptoms through increasing the content of DA in brain?Whether it can also effect other monoamine neurotransmitters?and what is its mechanism?These questions need to be further discussed.ObjectiveThe study was designed to explore the effects of ?-asarone on behavioral tests and monoamine neurotransmitters in chronic unpredictable mild stress(CUMS)mouse model.MethodsAnimals were randomly divided into 6 groups with 12 animals per group,including Control group,CUMS group,?-asarone 7.5 mg/kg group,?-asarone 15 mg/kg group,?-asarone 30 mg/kg group and fluoxetine 8 mg/kg group.The mice were under the CUMS protocol,meanwhile,the mice were respectively treated with ?-asarone(7.5,15 and 30mg/kg)and fluoxetine(8mg/kg)for 6 weeks.Behavioral tests,including sucrose preference test,forced swim test and open-field test,were performed to evaluate the antidepressant effects of ?-asarone.The concents of 5-HT,5-HIAA,DA,DOPAC,HVA,NE in the cortex,hippocampus,midbrain,striatum and serum of mice were determined by high performance liquid chromatography with fluorimetric detection(HPLC-FD).Furthermore,the concentrations of Trp,TPH,5-HTP,TDC and MAOA in mice cerebral cortex and midbrain were determined by ELISA.Results1.Effects of ?-asarone on behavioral tests in CUMS miceAt the beginning of the experiment,there were no significant differences in behavioral tests among groups(P>0.05).Through 3 weeks of continuous unpredictable stimulations,compared with the normal group,the sucrose preference percentage of the model group significantly reduced(P<0.01),the swimming immobility time significantly increased(P<0.01),the numbers of rearings were significantly lower(P<0.01);Compared with the model group,the sucrose preference percentage of the ?-asarone 30mg/kg group and fluoxetine 8mg/kg group significantly increased(P<0.05 or P<0.01),and the swimming immobility time of the P-asarone 30mg/kg group significantly decreased(P<0.05).After 6-weeks of CUMS,compared with the normal group,the sucrose preference percentage of the model group significantly reduced(P<0.01),the swimming immobility time significantly increased(P<0.01),the numbers of crossings and rearings were significantly lower(P<0.01);the difference was significant(P<0.05);Compared with the model group,the sucrose preference percentage of the p-asarone(15,30mg/kg)group and fluoxetine 8mg/kg group significantly increased(P<0.01),and the swimming immobility time significantly decreased(P<0.01),the numbers of crossings and rearings in?-asarone 30mg/kg group and fluoxetine 8mg/kg group were significantly increased(P<0.05).2.Effects of ?-asarone on the concentration of neurotransmitters in CUMS miceCompared with the normal group,the concentrations of 5-HT,HIAA and DA in cortex,midbrain,striatum and serum of model group showd significantly decrease(P<0.05 or P<0.01),and the contents of DA and NE in hippocampus were significant lower(P<0.05);compared with the model group,the levels of 5-HT,5-HIAA and DA in the cortex,midbrain,striatum and serum of CUMS mice in ?-asarone(15,30mg/kg)group and fluoxetine 8mg/kg group were significantly increased(P<0.05 or P<0.01),the content of DA of hippocampus in ?-asarone 30mg/kg group was significant inreased(P<0.05)· There were no significant differences in the concentrations of DOPAC and HVA among groups(P>0.05).3.Effects of ?-asarone on the 5-HT system in CUMS miceThere were no significant differences in Trp,TDC and MAOA in the cortex and midbrain among groups(P>0.05).Compared with the normal group,the levels of TPH and 5-HTP of cortex and midbrain in model group showd significantly decrease(P<0.05 or P<0.01);compared with the model group,the levels of TPH and 5-HTP of cortex and midbrain in p-asarone 30mg/kg group were elevated significantly(P<0.05 or P<0.01).ConclusionThe successful mice CUMS model were established through 6 weeks of continuous unpredictable stimulation,and ?-asarone could reverse the CUMS-induced behavioral abnormalities and exerts comparable antidepressant-like effects to that of fluoxetine in CUMS mice,which may be related to ?-asarone can increase the contents of 5-HT,5-HIAA and DA in the cortex,midbrain,striatum and serum of CUMS model mice.We deduced that?-asarone may firstly improve the expression of TPH,and then increase the level of 5-HTP,which further led to a rise in the concentration of 5-HT.