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The existing treatment methods have limitations, such as poor adherence and inability to completely avoid relapse. Histidine triad nucleotide\u2010binding protein 1 (HINT1) is involved in many neuropsychiatric diseases, such as schizophrenia, pain, and drug dependence. Studies have confirmed that there is a genetic link between HINT1 and addictions such as nicotine and cocaine. However, there is no research on the role of HINT1 protein in morphine addiction at home and abroad. Thus, we designed this project by constructing different types of morphine addiction animal models, including conditioned place preference and behavioral sensitization. We comprehensively examined the participation of HINT1 protein in key brain regions associated with addiction, including prefrontal cortex, nucleus accumbens, corpus striatum, and hippocampus, in different stages of different models. In addition, we used HINT1 knockout mice to establish the above models and physical dependence model to investigate the effect of HINT1 protein deletion on morphine addiction\u2010related behaviors. We found that HINT1 has varying degrees of involvement in different stages of multiple addictive animal models. The absence of HINT1 can attenuate morphine\u2010mediated addictive behavior to a certain extent and can alleviate the withdrawal symptoms of morphine.<\/jats:p>","DOI":"10.1111\/adb.12897","type":"journal-article","created":{"date-parts":[[2020,3,14]],"date-time":"2020-03-14T21:11:11Z","timestamp":1584220271000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["The role of HINT1 protein in morphine addiction: An animal model\u2010based study"],"prefix":"10.1111","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3290-3768","authenticated-orcid":false,"given":"Peng","family":"Liu","sequence":"first","affiliation":[{"name":"College of Medicine and Forensics, Key Laboratory of the Health Ministry for Forensic Medicine, Key Laboratory of Environment and Genes Related to Diseases of the Education Ministry Xi'an Jiaotong University Health Science Center  Xi'an 710061 China"},{"name":"Department of 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