Effects of Banxia Shumi (半夏秫米) Decoction on Hypothalamic 5-HT-Mediated cAMP/CREB/BDNF Pathway in Insomniac Rats
Objective:To investigate the effects of Banxia Shumi (半夏秫米) Decoction on the behavior and hypothalamic 5-hydroxytryptamine (5-HT)-mediated cyclic adenosine monophosphate (cAMP)/cAMP response element-binding protein (CREB)/brain-derived neurotrophic factor (BDNF) pathway in insomnia model rats.Methods:SD rats were randomly divided into a normal control group,a model control group,Banxia Shumi Decoction groups (8.1,16.2,32.4 g/kg),and a diazepam group (0.9 mg/kg).Except for the normal control group,all rats were treated with para-chlorophenylalanine (PCPA) to establish an insomnia model.After 7 days of oral administration of corresponding drugs or distilled water,behavior tests,including the pentobarbital sodium sleep test,open field test,and Morris water maze test,were performed.En-zyme-linked immunosorbent assay (ELISA) was used to detect the levels of 5-HT,adenylate cyclase (AC),and cAMP in the hypothalamus.Western blot was used to measure the protein expression of hypothalamic 5-HT1AR,5-HT2AR,protein kinase A (PKA),p-cAMP response ele-ment-binding protein (p-CREB),CREB,and brain-derived neurotrophic factor (BDNF).Results:Compared with the normal control group,the model control group showed significant increases in sleep latency,immobility time,fecal pellet count,total swimming distance,and escape latency in the water maze,while the sleep duration,average speed,central grid crossings,total activity distance,target quadrant crossings,and time spent in the target quadrant were significantly decreased.The levels of 5-HT,AC,and cAMP in the model control group were significant-ly reduced,and the protein expressions of 5-HT1AR,PKA,p-CREB,and BDNF were significantly downregulated (P<0.01).Compared with the model control group,the Banxia Shumi Decoction groups significantly reduced sleep latency,immobility time,fecal pellet count,escape la-tency,and total swimming distance,while increasing sleep duration,average speed,central grid crossings,total activity distance,target quadrant crossings,and time spent in the target quadrant.The levels of 5-HT,AC,and cAMP were elevated,and the protein expression of 5-HT1AR,PKA,p-CREB,and BDNF was upregulated (P<0.05 or P<0.01).Conclusion:Banxia Shumi Decoction can improve sleep,reduce anxiety,and enhance learning and memory abilities in insomnia model rats by activating the hypothalamic 5-HT and 5-HT1AR-mediated cAMP/CREB/BDNF pathways.
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