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A morphine/heroin vaccine with new hapten design attenuates behavioral effects in rats
Li, Qian-Qian1; Luo, Yi-Xiao1; Sun, Cheng-Yu1; Xue, Yan-Xue1; Zhu, Wei-Li1; Shi, Hai-Shui1; Zhai, Hai-Feng1; Shi, Jie1; Lu, Lin1,2
关键词addiction immunization morphine heroin vaccine
刊名JOURNAL OF NEUROCHEMISTRY
2011-12-01
DOI10.1111/j.1471-4159.2011.07502.x
119期:6页:1271-1281
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Biochemistry & Molecular Biology ; Neurosciences
资助者Natural Science Foundation of China ; Beijing Municipal Natural Science Foundation ; Natural Science Foundation of China ; Beijing Municipal Natural Science Foundation
研究领域[WOS]Biochemistry & Molecular Biology ; Neurosciences & Neurology
关键词[WOS]NUCLEUS-ACCUMBENS DOPAMINE ; ACTIVE IMMUNIZATION ; INDUCED REINSTATEMENT ; HEROIN-ADDICTION ; COCAINE SEEKING ; MAINTENANCE ; DEPENDENCE ; RELAPSE ; OPIATE ; METHAMPHETAMINE
英文摘要

Heroin use has seriously threatened public heath in many countries, but the existing therapies continue to have many limitations. Recently, immunotherapy has shown efficacy in some clinical studies, including vaccines against nicotine and cocaine, but no opioid vaccines have been introduced in clinical studies. The development of a novel opioid antigen designed specifically for the prevention of heroin addiction is necessary. A morphinekeyhole limpet hemocyanin conjugate was prepared and administered subcutaneously in rats. Antibody titers in plasma were measured using an enzyme-linked immunosorbent assay (ELISA). Competitive ELISA was used to assess the selectivity of the antibodies. Dopamine concentrations in the nucleus accumbens in rats after vaccine administration were determined by high-performance liquid chromatography with electrochemical detection. The effects of the vaccine on the heroin-primed restatement of self-administration and locomotor sensitization were evaluated. A novel hapten, 6-glutarylmorphine, was produced, and the vaccine generated a high antibody titer response. This vaccine displayed specificity for both morphine and heroin, but the anti-morphine antibodies could not recognize dissimilar therapeutic opioid compounds, such as buprenorphine, methadone, naloxone, naltrexone, codeine, and nalorphine. The morphine antibody significantly decreased morphine-induced locomotor activity in rats after immunization. Importantly, rats immunized with this vaccine did not exhibit heroin-primed reinstatement of heroin seeking when antibody levels were sufficiently high. The vaccine reduced dopamine levels in the nucleus accumbens after morphine administration, which is consistent with its behavioral effects. These results suggest that immunization with a novel vaccine is an effective means of inducing a morphine-specific antibody response that is able to attenuate the behavioral and psychoactive effects of heroin.

语种英语
所属项目编号30725016 ; 31070958 ; 7091003
资助者Natural Science Foundation of China ; Beijing Municipal Natural Science Foundation ; Natural Science Foundation of China ; Beijing Municipal Natural Science Foundation
WOS记录号WOS:000297948800012
引用统计
被引频次:27[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/62215
专题中国药物依赖性研究所
作者单位1.Minist Hlth, Minist Educ, Key Lab Neurosci, Beijing, Peoples R China
2.Peking Univ, Natl Inst Drug Dependence, Beijing 100191, Peoples R China
推荐引用方式
GB/T 7714
Li, Qian-Qian,Luo, Yi-Xiao,Sun, Cheng-Yu,et al. A morphine/heroin vaccine with new hapten design attenuates behavioral effects in rats[J]. JOURNAL OF NEUROCHEMISTRY,2011,119(6):1271-1281.
APA Li, Qian-Qian.,Luo, Yi-Xiao.,Sun, Cheng-Yu.,Xue, Yan-Xue.,Zhu, Wei-Li.,...&Lu, Lin.(2011).A morphine/heroin vaccine with new hapten design attenuates behavioral effects in rats.JOURNAL OF NEUROCHEMISTRY,119(6),1271-1281.
MLA Li, Qian-Qian,et al."A morphine/heroin vaccine with new hapten design attenuates behavioral effects in rats".JOURNAL OF NEUROCHEMISTRY 119.6(2011):1271-1281.
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