A morphine conjugate vaccine attenuates the behavioral effects of morphine in rats.
A morphine conjugate vaccine attenuates the behavioral effects of morphine in rats.
复制标题
吗啡偶联疫苗会减弱吗啡在大鼠中的行为影响。
DOI：
10.1016/j.pnpbp.2013.05.012
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发表时间：
2013-08-01
影响因子：
5.6
通讯作者：
Kosten, Thomas R.
中科院分区：
文献类型：
--
作者：
Kosten, Therese A.;Shen, Xiaoyun Y.;O'Malley, Patrick W.;Kinsey, Berma M.;Lykissa, Ernest D.;Orson, Frank M.;Kosten, Thomas R.
阿片类药物依赖疫苗可以提供一种治疗方法，减少或减缓药物向大脑的分布，从而减少药物的强化作用。我们测试了给大鼠注射吗啡结合疫苗（keyhole limpet hemocyanin-6-琥珀基吗啡；KLH-6-SM）是否会产生抗体，并显示出对吗啡或其他海洛因代谢物的特异性。采用抗伤性和条件位置偏好（CPP）试验对疫苗的功能效果进行了检验。大鼠要么接种了KLH-6- sm，并在3周和16周后接受两次强化，要么作为对照，单独接受KLH。接种大鼠产生抗吗啡抗体；浓度升高，并在24周内维持在中等水平。竞争性抑制ELISA结果表明，游离吗啡和其他海洛因代谢物可抑制抗体结合。接种疫苗的大鼠在第4周至第6周的测试中显示吗啡CPP降低，在第7周的测试中显示对吗啡的抗伤害性反应降低。使用气相色谱-质谱联用（GC-MS）对26周时获得的样本进行评估，接种疫苗的大鼠的脑吗啡水平显著降低。这表明吗啡进入大脑的速度减少或减慢了。这些结果支持KLH-6-SM作为阿片类药物依赖的候选疫苗。
Vaccines for opioid dependence may provide a treatment that would reduce or slow the distribution of the drug to brain, thus reducing the drug's reinforcing effects. We tested whether a conjugate vaccine against morphine (keyhole limpet hemocyanin-6-succinylmorphine; KLH-6-SM) administered to rats would produce antibodies and show specificity for morphine or other heroin metabolites. The functional effects of the vaccine were tested with antinociceptive and conditioned place preference (CPP) tests. Rats were either vaccinated with KLH-6-SM and received two boosts 3 and 16 weeks later or served as controls and received KLH alone. Anti-morphine antibodies were produced in vaccinated rats; levels increased and were sustained at moderate levels through 24 weeks. Antibody binding was inhibited by free morphine and other heroin metabolites as demonstrated by competitive inhibition ELISA. Vaccinated rats showed reduced morphine CPP, tested during weeks 4 to 6, and decreased antinociceptive responses to morphine, tested at week 7. Brain morphine levels, assessed using gas-chromatography coupled to mass spectrometry (GC–MS) on samples obtained at 26 weeks, were significantly lower in vaccinated rats. This suggests that morphine entry into the brain was reduced or slowed. These results provide support for KLH-6-SM as a candidate vaccine for opioid dependence.
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影响因子：
3.2
作者：
Stotts AL;Dodrill CL;Kosten TR
通讯作者：
Kosten TR
影响因子：
10.6
作者：
Haney, Margaret;Gunderson, Erik W.;Jiang, Huiping;Collins, Eric D.;Foltin, Richard W.
通讯作者：
Foltin, Richard W.
影响因子：
5.8
作者：
Selley, DE;Cao, CC;Childers, SR
通讯作者：
Childers, SR
影响因子：
--
作者：
Martell, Bridget A.;Orson, Frank M.;Poling, James;Mitchell, Ellen;Rossen, Roger D.;Gardner, Tracie;Kosten, Thomas R.
通讯作者：
Kosten, Thomas R.
影响因子：
56.9
作者：
BERKOWITZ, B;SPECTOR, S
通讯作者：
SPECTOR, S