Objective: To determine the mechanisms underlying the anti-depressant effects of Kaixin Jieyu Decoction (, 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(-1) of 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-HT1A and 5-HT2A receptor 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-HT2A receptor mRNA expression. In contrast, they showed a significant increase in 5-HT1A receptor mRNA expression in the cerebral cortex. In the hippocampus, 5-HT1A receptor mRNA expression was lower whereas 5-HT2A receptor 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-HT1A and 5-HT2A receptor expression in rat cerebrum, and this may be one of mechanisms of antidepressant effects of KJD.
Keywords: Kaixin Jieyu Decoction; behavior; depression; monoamines neurotransmitter; serotonin1A and serotonin2A receptor mRNA.