Effects and Mechanisms of Wendan Decoction on Anxiety,Fear,and Insomnia in the Rat Model of Insomnia Due to Heart-Gallbladder Qi Deficiency.

Objective To explore the effects and mechanisms of Wendan Decoction(WDT)on anxiety-like and fear-like behaviors,as well as sleep,in the rat model of insomnia due to heart-gallbladder qi deficiency. Methods SD male rats were randomly allocated into blank,model,Anshen Dingzhi pills(0.54 g/kg),low-,medium-,and high-dose(8.7,17.4,and 34.8 g/kg)WDT groups.Plantar electric stimulation combined with forced exercise was used for modeling,and the rats were administrated with corresponding agents by gavage for 7 consecutive days after the modeling.Behavioral tests were performed,and the c-Fos protein level,neuron firing rate,and hippocampal neurotransmitter content in brain regions were determined. Results Compared with the model group,medium-dose WDT shortened the avoidance time,freezing time,and sleep latency(P<0.001,P<0.001,P=0.010).Furthermore,medium-dose WDT attenuated the elevated c-Fos expression in emotion-related brain regions,including the prelimbic cortex(P<0.001),infralimbic cortex(P<0.001),basolateral amygdala(P<0.001),central amygdala(P<0.001),ventral hippocampus(P=0.004),periaqueductal gray(P<0.001),and dorsal raphe nucleus(P<0.001),as well as the increased firing rate of ventral hippocampal interneurons(P=0.005).In addition,it reduced the hippocampal glutamate content and the glutamate/gamma-aminobutyric acid ratio(P<0.001,P=0.013). Conclusions WDT can reduce the excitatory drive of glutamic acid to interneurons by inhibiting the release of glutamic acid from pyramidal neurons of ventral hippocampus,thus playing a role in improving sleep and mitigating the anxiety-like,fear-like,and depression-like behaviors in the rat model of insomnia due to heart-gallbladder qi deficiency.