PMID- 30984042 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220410 IS - 1664-0640 (Print) IS - 1664-0640 (Electronic) IS - 1664-0640 (Linking) VI - 10 DP - 2019 TI - SiNiSan Ameliorates the Depression-Like Behavior of Rats That Experienced Maternal Separation Through 5-HT1A Receptor/CREB/BDNF Pathway. PG - 160 LID - 10.3389/fpsyt.2019.00160 [doi] LID - 160 AB - Background: Early adverse life stress is an important dangerous factor in the development of psychiatric disorders, particularly depression. Available clinical antidepressant agents, such as fluoxetine, [a selective serotonin reuptake inhibitor (SSRI)], are unsatisfactory because of their side effects. SiNiSan (SNS) is a classic Chinese medicine prescription regarded to disperse stagnated liver qi to relieve qi stagnation. Therefore, this study was designed to detect the effects and molecular mechanism of SNS treatment in rats subjected to maternal separation (MS). Method: Male neonatal Wistar rats were divided into six groups including control + ddH(2)O, MS + ddH(2)O, MS + fluoxetine (5 g/kg), MS + SNS -low dose (2.5 g/kg), MS + SNS -medium dose (5 g/kg), MS + SNS -high dose (10 g/kg). The volume of drugs and ddH2O in each group are according to the weight of rats every day (10 mL/kg). Each group comprised 16 pups with 8 young and 8 adult pups. Except for the control group, all MS groups were separated from their mothers for 4 h/day from 9:00 to 13:00 during postnatal days (PNDs) 1 to 21. After MS, the six groups were intragastrically administered with ddH2O, fluoxetine, and different doses of SNS until PND 28 (for young pups) and PND 56 (for adult pups). The pups were weighed every day, and depression-like behavior was assessed by sucrose preference test, open field test, and forced swimming test. Serotonin 1A (5-HT1A) receptor, phosphorylated protein kinase A (p-PKA) substrate, cAMP response element-binding protein (CREB), p-CREB and brain-derived neurotrophic factor (BDNF) in the hippocampus were examined by Western blot, and in situ 5-HT1A receptor expression was measured by IHC. Results: Young and adult MS rats exhibited depression-like behavior. However, the depression-like behavior was ameliorated by SNS in both age groups. The levels of 5-HT1A receptor, p-CREB, and BDNF in the hippocampus were reduced in young and adult MS rats. SNS treatment significantly up-regulated the expression of 5-HT1A receptor, p-CREB, and BDNF in the hippocampus of adult MS rats. However, few significant effects on the protein expression were observed in the young MS rats. Conclusion: MS in infancy could develop depression-like behavior in young and adult. SNS treatment may perform antidepressant effects on young and adult MS rats through the BDNF/PKA/CREB pathway. FAU - Cao, Kerun AU - Cao K AD - School of Fundamental Medical Science, Guangzhou University of Chinese Medicine, Guangzhou, China. FAU - Shen, Chongkun AU - Shen C AD - School of Fundamental Medical Science, Guangzhou University of Chinese Medicine, Guangzhou, China. FAU - Yuan, Yumei AU - Yuan Y AD - Shenzhen Baoan Hospital of Chinese Medicine, Shenzhen, China. FAU - Bai, Shasha AU - Bai S AD - Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou, China. FAU - Yang, Lei AU - Yang L AD - Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou, China. FAU - Guo, Lili AU - Guo L AD - Third Affiliated Hospital of Henan University of Chinese Medicine, Henan University of Chinese Medicine, Zhengzhou, China. FAU - Zhang, Rong AU - Zhang R AD - Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou, China. FAU - Shi, Yafei AU - Shi Y AD - School of Fundamental Medical Science, Guangzhou University of Chinese Medicine, Guangzhou, China. LA - eng PT - Journal Article DEP - 20190328 PL - Switzerland TA - Front Psychiatry JT - Frontiers in psychiatry JID - 101545006 PMC - PMC6447714 OTO - NOTNLM OT - SiNiSan OT - brain-derived neurotrophic factor OT - depression OT - early life stress OT - serotonin 1A receptor EDAT- 2019/04/16 06:00 MHDA- 2019/04/16 06:01 PMCR- 2019/03/28 CRDT- 2019/04/16 06:00 PHST- 2018/09/14 00:00 [received] PHST- 2019/03/04 00:00 [accepted] PHST- 2019/04/16 06:00 [entrez] PHST- 2019/04/16 06:00 [pubmed] PHST- 2019/04/16 06:01 [medline] PHST- 2019/03/28 00:00 [pmc-release] AID - 10.3389/fpsyt.2019.00160 [doi] PST - epublish SO - Front Psychiatry. 2019 Mar 28;10:160. doi: 10.3389/fpsyt.2019.00160. eCollection 2019.