| Objective:To study the antidepressant effect and discuss the function mechanism of Oleoylethanolamide(OEA).Method:1 The mice were randomly divided:solvent control group,chlorine meters(10 mg/kg)group,OEA groups(1.5,3,6 mg/kg),all groups were administered ig for 7 days,The tail suspension test(TST).forced swimming test(FST)?open field activity t est were carried out to examine the antidepressant effect of OEA in mice.Respectively i mmobility time,locomotor activity as the evaluation index.2 The mice were randomly divided:solvent control group,model group,imipramine group(5 mg/kg)group,OEA groups(1.5,3,6 mg/kg).Chronic unpredictable mild stress(CUMS)model is established.In addition to the solvent control group,the remaining fiv e groups of mice were undergoing four weeks of chronic unpredictable mild stress,after modeling one week of each group,each group were ig administered for three weeks.T o measure the body weight of mice on the 7th?14th?21st and 28th day during experim ents respectively,and at the same time,open-field test,sucrose consumption test,rectal temperature detection and morris water maze test were conducted.The end of the behavi oral,take the blood from the eyeball,the brain,the left and right adrenal.3 To study the antidepressant mechanism of OEA by detecting the content of 5-sero tonin(5-HT),noradrenaline(NE)and monoamine oxidasecontent(MAO)in brain tissue com bined with inhibiting reuptake of monoamine(norepinephrine)test and reserpine test.4 To study the antidepressant mechanism of OEA by detecting adrenal index and th e content of adreno-cortico-tropic-hormone(ACTH).corticosterone(CORT)in the plasma.Results:(1)In the tail suspension test,administered continuously for 7 days,compa red with the solvent control group,OEA(6 mg/kg)group and clomipramine(10 mg/kg)mice tail suspension does not immobility time was significantly shorter(P<0.05).In the Forced swimming test,administered continuously for 7 days,compared with the solvent control group,OEA(6 mg/kg)group and clomipramine(10 mg/kg)mice forced swimmin g immobility time was significantly shortened(P<0.05).In Open-field test,compared with the solvent control group,clomipramine(10 mg/kg)group and OEA(with 1.5,3,6 mg/kg)dose group there was no significant difference(P>0.05).(2)The effects of OEA on body weight of CUMS mice by repeated measurement a nalysis,on 7,14,21,28 days,the weight of solvent control group mice changes gradual 1y increased.Imipramine group and OEA groups at 7,14,21,28 days compared with so lvent control group,showed a relatively low degree of weight gain,and on the 21th day of the experiment,compared with the solvent control group,model group and OEA(1.5 mg/kg)body weight of mice was significantly lower(P<0.05);on the 28th days of the experiment,compared with the solvent control group,model group and OEA(1.5 mg/kg)body weight of mice was significantly lower(P<0.05),compared with model group,OE A(6 mg/kg)body weight of mice was significantly higher(P<0.05).In open-field test,o n the 21th day of experiment,compared with the solvent control group,model group we re rearing significantly lower(P<0.05).on the 28th days of the experiment,compared wi th the solvent control group,model group were horizontal cross-bars and rearing were si gnificantly lower(P<0.05);compared with the model group,imipramine(5 mg/kg)group mice the level of cross-bars and rearing were significantly increased(P<0.05),compared with model group,OEA(with 1.5,3,6 mg/kg)mice level cross-bars and rearing were significantly increased(P<0.05).In Sucrose consumption test on the 21th day of experime nt,compared with the solvent control group,model group were absolute sucrose water in take significantly lower(P<0.05),show that the the CUMS model mouse euphoria missin g,in a state of depression;on the 28th days of the experiment,compared with the solve nt control group,model group were absolute sucrose water intake significantly reduced(P<0.05),compared with the model group,the imipramine group(5 mg/kg)and OEA(6 mg/kg)group the absolute amount of sucrose drinking water of the mice was significantl y higher(P<0.05).on the 21th day of experiment,compared with the solvent control gro up,model group mice relative sucrose water intake significantly reduced,but no significa nt difference compared with the model group,imipramine group(5 mg/kg)and OEA dos e group the relative sucrose water intake has increased,but no significant difference;on the 28th days of the experiment,the model mice relative the sucrose water intake compa red with the solvent control group with significant difference(P<005),imipramine group(5mg/kg)the OEA(6mg/kg)group mice relative to the sucrose water intake with the mo del group was significant difference(P<0.05).In the the CUMS model rectal temperature detection,on the 21th day of experiment,compared with the solvent control group,mod el group and OEA(1.5mg/kg)mice rectal temperature significantly lower(P<0.05);on th e 28th day of experimen,compared with the solvent control group,model group,OEA(1.5mg/kg)and OEA(3mg/kg)mice rectal temperature significantly lower(P<0.05),comp ared with the model group,imipramine triazine group(5mg/kg)and OEA(6 mg/kg)rect al temperature of mice was significantly higher(P<0.05).Morris water maze test,on the 21th day of experiment,compared with model group,solvent control group,OEA(6 m g/kg)mice escape latency was significantly shorter(P<0.05);on the 28th day of experime n,compared with the solvent control group,model group and small dose group(1.5 mg/kg)in mice escape latency was significantly longer(P<0.05),compared with model group,imipramine triazine group(5mg/kg)and OEA(6 mg/kg)in mice escape latency was signif icantly shorter(P<0.05).(3)The levels of monoamine neurotransmitter in brain tissue detection experiment sh owed:compared with the model group,clomipramine(5 mg/kg)group and OEA group(6 mg/kg)of norepinephrine(NE)were significantly increased(P<0.05);compared with the modelgroup,clomipramine(5 mg/kg)group,OEA(3 mg/kg)group and the OEA(6 mg/kg)group of 5-hydroxytryptamine(5-HT)were significantly increased(P<0.05).In rese rpine Antagonize the temperature drops test,compared with the solvent control group,cl omipramine(10 mg/kg)group 3h,4h,5h and OEA(6 mg/kg)group in 4h,5h could sig nificantly antagonize the reserpine-induced hypothermia in mice(P<0.05).By detecting brai n monoamine oxidase(MAO),compared with the solvent control group in the mice brai n MAO was significantly increased(P<0.05);compared with model group,OEA(6mg/k g)mice brain MAO was significantly lower(P<0.05).(4)In the test of OEA effect on HPA axis of CUMS model mice,mainly detect thr ee aspects:adrenal gland weight(absolute weight and relative weight),ACTH,CORT co ntent in serum.The results showed:on the 28th day,compared with the solvent control group,model group were absolute adrenal weight and relative adrenal weight were signifi cantly increased(P<0.05),Compared with model group,imipramine(5 mg/kg)group and OEA(6 mg/kg)mice adrenal absolute weight was significantly lower(P<0.05),imipram ine(5 mg/kg)group,OEA(mg/kg)group and OEA(6 mg/kg)mice relative adrenal wei ght significantly reduced(P<0.05);Compared with the solvent control group,model grou p was significantly increased(P<0.05),compared with the model group,imipramine group(5 mg/kg),OEA(3 mg/kg)group and the OEA(6 mg/kg)group CORT content was si gnificantly lowe(P<0.05)r;Similarly;Compared with the solvent control group,model gro up ACTH was significantly increased(P<0.05),compared with model group,imipramine g roup(5 mg/kg),OEA(3 mg/kg)group and the OEA(6 mg/kg)group ACTH content wa s significantly lowe(P<0.05)r.Conclusion:OEA could significantly improve depression-like behavior in mice,the mechanism of antidepressant may be related with affection the monoamine neurotransmitt er metabolism and normalize the HPA axis function. |
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