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Study On Orphanin-FQ In The Treatment Of Alcohol Addiction

Posted on:2024-09-30Degree:MasterType:Thesis
Country:ChinaCandidate:W C ZhangFull Text:PDF
GTID:2531307091473334Subject:Pharmaceutical engineering
Abstract/Summary:PDF Full Text Request
Alcohol addiction,also known as alcohol use disorder(AUD),is the third largest global public health problem.There is currently no safe and effective drug treatment for alcohol addiction.Orphanin-FQ,as an endogenous polypeptide,has a significant effect on drug dependence and addiction.Therefore,the purpose of this study is to explore the use of orphanin-FQ in the treatment of alcohol addiction.The study established alcohol addiction model by given the C57BL/6N mice intermittent alcohol,and the alcohol preference test,open field and elevated cross test were used to evaluate the model and drug efficacy.The results showed that the alcohol-addicted mice had apparent preference for alcohol and anxiety symptoms after withdrawal,and the mice with intrathecal injection of orphanin-FQ had significantly lower alcohol preference and anxiety symptoms after alcohol withdrawal.Elisa,immunofluorescence staining,RT-q PCR and Western blot were used to explore the mechanism of orphanin-FQ’s treatment for alcohol addiction.It was found that orphaninFQ’s treatment reduced the production of cyclic adenosine monophosphate(c AMP)and downregulated the phosphorylation level of c AMP-response element binding protein(CREB)in the brain of alcohol-addicted mice,and then reduced the production of corticotropin releasing hormone(CRF)in hypothalamus of the mice,and finally decreased the secretion of corticosterone(CORT)in the body,thus improving the anxiety symptoms of mice after alcohol withdrawal.In addition,the study established alcoholaddicted rhesus monkey model and found that alcohol-addicted rhesus monkey showed the impairment of cognitive control through cognitive reversal experiment,and this laid a important foundation for further studying the effect and mechanism of orphanin-FQ’s treating alcohol addiction in nonhuman primates.This study initially clarified the therapeutic effect and mechanism of orphanin-FQ’s treatment for alcohol addiction.It provided theoretical support for orphanin-FQ in the treatment of alcohol addiction,laid a foundation for orphanin-FQ’s effective development and efficient utilization,and added a new option for the development of alcohol addiction treatment drugs.Thus,the study has important scientific significance and extensive application value.
Keywords/Search Tags:Alcohol addiction model, Orphanin-FQ, CRF, CREB, Cognitive flexibility
PDF Full Text Request
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