title: AUTS2 in the nucleus accumbens is essential for heroin-induced behavioral sensitization.
abstract: Autism susceptibility candidate 2 (AUTS2) is a gene associated with autism and mental retardation. Recent studies have suggested an association of the AUTS2 gene with heroin dependence, and reduced AUTS2 gene expression may confer increased susceptibility to heroin dependence. However, the functional role of the AUTS2 protein in regulating enduring neuroadaptations in response to heroin exposure has not been established. Here, we investigated the effects of acute and chronic heroin exposure on AUTS2 mRNA and protein expression in the nucleus accumbens (NAc) and caudate-putamen (CPu) to determine whether changes in AUTS2 expression are associated with heroin-induced locomotor sensitization in mice. Moreover, we explored whether AUST2 knockdown affects heroin-induced locomotor sensitization. AUTS2 mRNA and protein expression in the NAc, but not the CPu, was decreased after chronic heroin (1mg/kg) administration. In the NAc, the expression of heroin-induced locomotor sensitization was enhanced through the lentiviral-AUTS2-shRNA-mediated knockdown of AUTS2, while the overexpression of AUTS2 attenuated the locomotor-stimulant effects of heroin. Together, these results indicate that AUTS2 in the NAc, but not the CPu, suppresses the initiation and expression of heroin-induced behavioral sensitization, suggesting that AUST2 may be a potential target for the treatment of heroin dependence.
authors.affiliation: College of Forensic Science, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Xi'an Mental Health Center, Xi'an, Shannxi 710061, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Xing
authors.affiliation: Xi'an Mental Health Center, Xi'an, Shannxi 710061, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Dang
authors.affiliation: College of Forensic Science, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Ji
authors.affiliation: College of Forensic Science, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China; Key Laboratory of Ministry of Public Health for Forensic Science, Xi'an, Shaanxi 710061, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Yan
authors.affiliation: College of Forensic Science, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
authors.forename: Yunxiao
authors.initials: Y
authors.lastname: Li
authors.affiliation: College of Forensic Science, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China; Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education, Xi'an, Shaanxi 710061, China.
authors.forename: Xiaomeng
authors.initials: X
authors.lastname: Qiao
authors.affiliation: College of Forensic Science, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China; Key Laboratory of Ministry of Public Health for Forensic Science, Xi'an, Shaanxi 710061, China; Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education, Xi'an, Shaanxi 710061, China. Electronic address: aiwapeter@163.com.
authors.forename: Jianghua
authors.initials: J
authors.lastname: Lai
mesh_terms: D000818:Animals; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism; D003598:Cytoskeletal Proteins; D004195:Disease Models, Animal; D055785:Gene Knockdown Techniques; D003932:Heroin / Q000008:administration & dosage / Q000633:toxicity; D006556:Heroin Dependence / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009294:Narcotics / Q000008:administration & dosage / Q000633:toxicity; D009479:Neuropeptides / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D011699:Putamen / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D014157:Transcription Factors; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
chemical_list: C549397:Auts2 protein, mouse; D003598:Cytoskeletal Proteins; D009294:Narcotics; D009479:Neuropeptides; D009687:Nuclear Proteins; D012333:RNA, Messenger; C484602:Rac1 protein, mouse; D014157:Transcription Factors; D003932:Heroin; D020830:rac1 GTP-Binding Protein
keywords: autism susceptibility candidate 2; behavioral sensitization; nucleus accumbens