Inhibition of phosphodiesterase 2 ameliorates post-traumatic stress-induced alcohol intake disorder by regulating cAMP/cGMP signaling.

doi:10.1093/ijnp/pyac064

科研成果详情

题名	Inhibition of phosphodiesterase 2 ameliorates post-traumatic stress-induced alcohol intake disorder by regulating cAMP/cGMP signaling.
作者	Pan, Xiaoyu 1; Chen, Ling 2; Shan, Chunyan 3; Cai, Lisha4; Wang, Yue1; Chen, Yue 4; Gu, Ming4; Liu, Kaiping 4; Li, Pihong1; Pan, Jianchun4
发表日期	2022-11-17
发表期刊	The international journal of neuropsychopharmacology 影响因子和分区
语种	英语
原始文献类型	Article ; Early Access
关键词	alcohol intake cAMP/cGMP phosphodiesterase 2 post-traumatic stress single-prolonged stress
其他关键词	INVOLVEMENT ; PROTEIN ; MODEL
摘要	Post-traumatic stress disorder (PTSD) is the prevalent psychiatric disorders that induces alcohol use disorders (AUD) such as abnormal alcohol intake and anxiety. However, little is known about whether phosphodiesterase 2 (PDE2)-cAMP/cGMP signaling is involved in PTSD induced AUD., The present study used single-prolonged stress (SPS) to mimic PTSD that induced increases in ethanol intake and preference (two-bottle choice test) and anxiety-like behavior (elevated-plus maze test and novelty suppressed feeding test). PDE2 inhibitor Bay 60-7550 was administered to the mice and PKA inhibitor H89 and PKG inhibitor KT5823 were micro-injected into dorsolateral striatum (DLS) and central amygdala (CA) of mice to determine whether the effects of Bay 60-7550 on anxiety-like behavior in SPS mice are brain region dependent., PDE2 inhibitor Bay 60-7550 rescued SPS induced decreases in open arm entries and open arm time exposure in elevated-plus maze test and reversed increased latency to feed in the novelty suppressed feeding test. Moreover, SPS-induced ethanol use disorder was reversed by Bay 60-7550 as evidenced by decreased ethanol intake and preference without changing total fluid intake in the SPS mice after treatment with Bay 60-7550. However, Bay 60-7550 did not change the ethanol metabolism, the sucrose or quinine intake and preference. The locomotor activity was not affected after treatment with Bay 60-7550. Interestingly, Microinjection of PKA or PKG inhibitor H89 or KT5823 into DLS prevented the effects of Bay 60-7550 on alcohol intake and preference and cAMP-response element binding proteins phosphorylation (pCREB) and brain derived neurotrophic factor (BDNF) expression in DLS but not on the anxiety-like behavior in SPS mice; while Microinjection of these inhibitors into CA prevented Bay 60-7550-induced anxiolytic-like effects and pCREB and BDNF levels in CA but did not affect ethanol intake in SPS mice, indicating that the effects of Bay 60-7550 on different behavior are brain region-dependent., These findings support the hypothesis that PDE2-cAMP/cGMP signaling may differentially mediate PTSD-induced AUD and anxiety-like behavior.
资助项目	Natural Science Foundation of Zhejiang Province [LY21H310004]; Science and Technology Development Project of Wenzhou [Y20180818]; Zhejiang Provincial Public Welfare Research Project [2018C37082]; special scientific research fund project for Hospital Pharmacy of Zhejiang Pharmaceutical Association [2021ZYY05]
出版者	OXFORD UNIV PRESS
出版地	OXFORD
ISSN	1461-1457
EISSN	1469-5111
卷号	25 期号:11 页码:936-945
DOI	10.1093/ijnp/pyac064
页数	10
WOS类目	Clinical Neurology ; Neurosciences ; Pharmacology & Pharmacy ; Psychiatry
WOS研究方向	Neurosciences & Neurology ; Pharmacology & Pharmacy ; Psychiatry
WOS记录号	WOS:000871031000001
收录类别	PUBMED ; SCIE ; SCOPUS
URL	查看原文
PubMed ID	36124735
SCOPUSEID	2-s2.0-85142401789
通讯作者地址	[Li, Pihong]Department of General Surgery,The Second Affiliated Hospital of Wenzhou Medical University,109 West college Road, Zhejiang,Wenzhou,325027,China
Scopus学科分类	Medicine (all)
引用统计	被引频次[WOS]：0 [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/166692
专题	第二临床医学院、附属第二医院、育英儿童医院药学院（分析测试中心）附属第二医院其他_附属康宁医院（温州市康宁医院）
通讯作者	Li, Pihong
作者单位	1.Department of General Surgery,The Second Affiliated Hospital of Wenzhou Medical University,Wenzhou,China; 2.Department of Clinical Pharmacy,Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province,Affiliated Hangzhou First People’s Hospital,Zhejiang University School of Medicine,Hangzhou,China; 3.Clinical Research Center,The Affiliated Kangning Hospital of Wenzhou Medical University,Zhejiang Province,Wenzhou,China; 4.Brain Institute,School of Pharmacy,Wenzhou Medical University,Zhejiang Province,Wenzhou,China
第一作者单位	第二临床医学院，附属第二医院、育英儿童医院; 附属第二医院
通讯作者单位	第二临床医学院，附属第二医院、育英儿童医院; 附属第二医院
第一作者的第一单位	第二临床医学院，附属第二医院、育英儿童医院
推荐引用方式 GB/T 7714	Pan, Xiaoyu,Chen, Ling,Shan, Chunyan,et al. Inhibition of phosphodiesterase 2 ameliorates post-traumatic stress-induced alcohol intake disorder by regulating cAMP/cGMP signaling.[J]. The international journal of neuropsychopharmacology,2022,25(11):936-945.
APA	Pan, Xiaoyu., Chen, Ling., Shan, Chunyan., Cai, Lisha., Wang, Yue., ... & Pan, Jianchun. (2022). Inhibition of phosphodiesterase 2 ameliorates post-traumatic stress-induced alcohol intake disorder by regulating cAMP/cGMP signaling.. The international journal of neuropsychopharmacology, 25(11), 936-945.
MLA	Pan, Xiaoyu,et al."Inhibition of phosphodiesterase 2 ameliorates post-traumatic stress-induced alcohol intake disorder by regulating cAMP/cGMP signaling.".The international journal of neuropsychopharmacology 25.11(2022):936-945.