Effects of Kaixin Jieyu Decoction(开心解郁汤)on Behavior, Monoamine Neurotransmitter Levels, and Serotonin Receptor Subtype Expression in the Brain of A Rat Depression Model

【摘要】 Objective:To determine the mechanisms underlying the anti-depressant effects of Kaixin Jieyu Decoction（开心解郁汤,KJD）by investigating the effects of KJD on behavior,monoamine neurotransmitter levels,and serotonin（5-HT）receptor subtype expression in the brain in a rat model of depression.Methods:The rat depression model was established using chronic unpredictable mild stress（CUMS）.Forty-eight Sprague Dawley rats were randomly divided into control,depression model（CUMS）,CUMS±KJD(7.7 g/kg^-1·d^-1of crude drug),and CUMS+fluoxetine(2.4 mg/kg^-1·d^-1)groups（n=12 in each group）,and the treatments lasted for 21 days.We regularly evaluated body weight,sucrose consumption,and horizontal and vertical activity scores in open-field tests.The content of the monoamine neurotransmitters 5-HT,norepinephrine（NE）,and dopamine（DA）and the DA metabolite homovanillic acid in the cerebral cortex,and 5-HT_1Aand 5-HT_2Areceptor mRNA in the cerebral cortex and the hippocampus,were determined respectively by high-performance liquid chromatography-coularray electrochemical detector and real-time polymerase chain reaction.Results:Compared with the control group,CUMS rats showed a variety of depression-like behavioral changes,including a significant reduction in body weight,sucrose consumption,and horizontal and vertical activity scores in open-field tests（P<0.05 or P<0.01）,and a significant decrease in 5-HT and NE levels and 5-HT_2Areceptor mRNA expression.In contrast,they showed a significant increase in 5-HT_1Areceptor mRNA expression in the cerebral cortex.In the hippocampus,5-HT_1Areceptor mRNA expression was lower whereas 5-HT_2Areceptor mRNA expression was higher than in the control group（P<0.05 or P<0.01）.Treatment with KJD or fluoxetine partially attenuated these changes（P<0.05 or P<0.01）.Conclusion:KJD could normalize the levels of 5-HT and NE and adjust the balance of 5-HT_1Aand 5-HT_2Areceptor expression in rat cerebrum,and this may be one of mechanisms of antidepressant effects of KJD.更多还原

【Abstract】 Objective:To determine the mechanisms underlying the anti-depressant effects of Kaixin Jieyu Decoction（开心解郁汤,KJD）by investigating the effects of KJD on behavior,monoamine neurotransmitter levels,and serotonin（5-HT）receptor subtype expression in the brain in a rat model of depression.Methods:The rat depression model was established using chronic unpredictable mild stress（CUMS）.Forty-eight Sprague Dawley rats were randomly divided into control,depression model（CUMS）,CUMS±KJD(7.7 g/kg^-1·d^-1of crude drug),and CUMS+fluoxetine(2.4 mg/kg^-1·d^-1)groups（n=12 in each group）,and the treatments lasted for 21 days.We regularly evaluated body weight,sucrose consumption,and horizontal and vertical activity scores in open-field tests.The content of the monoamine neurotransmitters 5-HT,norepinephrine（NE）,and dopamine（DA）and the DA metabolite homovanillic acid in the cerebral cortex,and 5-HT_1Aand 5-HT_2Areceptor mRNA in the cerebral cortex and the hippocampus,were determined respectively by high-performance liquid chromatography-coularray electrochemical detector and real-time polymerase chain reaction.Results:Compared with the control group,CUMS rats showed a variety of depression-like behavioral changes,including a significant reduction in body weight,sucrose consumption,and horizontal and vertical activity scores in open-field tests（P<0.05 or P<0.01）,and a significant decrease in 5-HT and NE levels and 5-HT_2Areceptor mRNA expression.In contrast,they showed a significant increase in 5-HT_1Areceptor mRNA expression in the cerebral cortex.In the hippocampus,5-HT_1Areceptor mRNA expression was lower whereas 5-HT_2Areceptor mRNA expression was higher than in the control group（P<0.05 or P<0.01）.Treatment with KJD or fluoxetine partially attenuated these changes（P<0.05 or P<0.01）.Conclusion:KJD could normalize the levels of 5-HT and NE and adjust the balance of 5-HT_1Aand 5-HT_2Areceptor expression in rat cerebrum,and this may be one of mechanisms of antidepressant effects of KJD.更多还原