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A Conjugate Vaccine Attenuates Morphine- and Heroin-Induced Behavior in Rats
Li, Qian-Qian1,2,3; Sun, Cheng-Yu1,2; Luo, Yi-Xiao1,2; Xue, Yan-Xue2; Meng, Shi-Qiu1,2; Xu, Ling-Zhi1,2; Chen, Na2; Deng, Jia-Hui1,2; Zhai, Hai-Feng2; Kosten, Thomas R.5; Shi, Jie2; Lu, Lin1,2,4; Sun, Hong-Qiang1,4
关键词Drug Addiction Immunization Morphine Heroin Vaccine
刊名INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
2015-03-01
DOI10.1093/ijnp/pyu093
18期:5
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Clinical Neurology ; Neurosciences ; Pharmacology & Pharmacy ; Psychiatry
资助者National Science Technology Major Project ; Beijing Technological Innovation Base Project ; National Science Technology Major Project ; Beijing Technological Innovation Base Project
研究领域[WOS]Neurosciences & Neurology ; Pharmacology & Pharmacy ; Psychiatry
关键词[WOS]NUCLEUS-ACCUMBENS DOPAMINE ; BUPRENORPHINE TREATMENT ; MAINTENANCE TREATMENT ; INDUCED REINSTATEMENT ; SMOKING-CESSATION ; SIGNALING PATHWAY ; SUBSTANCE-ABUSE ; COCAINE SEEKING ; RELAPSE ; METHADONE
英文摘要

Background: Currently approved medications for opioid addiction have shown clinical efficacy, but undesired side effects, dependence induced by the medications themselves, and low treatment compliance necessitate the need for novel therapies.

Methods: A novel morphine-keyhole limpet hemocyanin conjugate vaccine was synthesized with 6-glutarylmorphine as the hapten and a lengthened linker of 6 carbon atoms. The titer and specificity of the triggered antibody were assessed by enzyme-linked immunosorbent assay. The effects of the vaccine on the morphine-induced elevation of dopamine levels in the nucleus accumbens were determined by high-performance liquid chromatography. The effects of the vaccine on morphine-induced locomotor sensitization and heroin-primed reinstatement of heroin self-administration were also assessed.

Results: After subcutaneous administration in rats, the vaccine triggered a high antibody titer, with comparable specificity for morphine, 6-acetylmorphine, and heroin, but no interaction with dissimilar therapeutic opioid compounds, including buprenorphine, naloxone, and nalorphine, was observed. The vaccine significantly prevented the elevation of dopamine levels in the nucleus accumbens induced by a single morphine challenge. Moreover, the vaccine prevented the expression of morphine-induced locomotor sensitization and heroin-primed reinstatement of heroin seeking, suggesting its potential for preventing relapse.

Conclusion: These results demonstrate that active immunization with the present vaccine induces a robust morphine/heroin-specific antibody response in rats and attenuates the behavioral effects of morphine and heroin.

语种英语
所属项目编号2013ZX09103003 ; Z131102002813096
资助者National Science Technology Major Project ; Beijing Technological Innovation Base Project ; National Science Technology Major Project ; Beijing Technological Innovation Base Project
WOS记录号WOS:000352538100012
Citation statistics
Cited Times:4[WOS]   [WOS Record]     [Related Records in WOS]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/54656
Collection北京大学精神卫生研究所
作者单位1.Peking Univ, Inst Mental Hlth, Hosp 6, Beijing 100191, Peoples R China
2.Peking Univ, Natl Inst Drug Dependence, Beijing 100191, Peoples R China
3.Natl Inst Food & Drug Control, Inst Food & Drug Safety Evaluat, Beijing, Peoples R China
4.Peking Univ, Minist Hlth, Key Lab Mental Hlth, Beijing 100191, Peoples R China
5.Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA
Recommended Citation
GB/T 7714
Li, Qian-Qian,Sun, Cheng-Yu,Luo, Yi-Xiao,et al. A Conjugate Vaccine Attenuates Morphine- and Heroin-Induced Behavior in Rats[J]. INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY,2015,18(5).
APA Li, Qian-Qian.,Sun, Cheng-Yu.,Luo, Yi-Xiao.,Xue, Yan-Xue.,Meng, Shi-Qiu.,...&Sun, Hong-Qiang.(2015).A Conjugate Vaccine Attenuates Morphine- and Heroin-Induced Behavior in Rats.INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY,18(5).
MLA Li, Qian-Qian,et al."A Conjugate Vaccine Attenuates Morphine- and Heroin-Induced Behavior in Rats".INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY 18.5(2015).
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