ABSTRACT
Depressive disorder (DD) is one of the typical affective disorders with a high morbidity, high suicide rate and high recurrence rate. Dysfunction of the 5hydroxytryptamine 1A receptor (5HT1AR) in the brain may serve an important role in the pathogenesis of DD. Currently, selective serotonin reuptake inhibitors are the first line antidepressants with 6070% efficacy and severe adverse effects. Previous studies have demonstrated that Chinese herbal medicines, including the Shuyu capsule (SYC), are effective antidepressants with few side effects. However, the mechanism remains unclear. In the present study, the effects of the SYC on the 5HT1AR level and the activation of adenylyl cyclasecyclic adenosine monophosphate (cAMP)protein kinase A (PKA)cAMP response elementbinding (CREB) signaling pathway that 5HT1AR mediates in the cells of hippocampal neurons were investigated in vitro. The SYC demonstrated an antidepressant effect similar to that of fluoxetine in a rat depression model. Treatment of hippocampal neurons with the serum of depressive rats resulted in a decrease in the 5HT1AR protein level and the activation of the cAMPPKACREB signaling pathway in hippocampal neurons. Exposure to the serum of rats that received chronic mild stress plus SYC treatment led to no alterations in the 5HT1AR level or the activation of the cAMPPKACREB signaling pathway compared with those of cells exposed to normal rat serum. This effect is similar to the effects of 5HT1AR antagonist WAY100635. In addition, the 5HT1A agonist 8hydroxy(dipropylamino) tetralin did not antagonize the effects of the SYC. Furthermore, the SYC exhibited an increased effect compared with fluoxetine on 5HT1AR levels and CREB activation. The present study suggested that the SYC functions by increasing 5HT1AR protein levels and the activation of the 5HT1ARmediated cAMPPKACREB signaling pathway in hippocampal neurons.
