A methamphetamine vaccine attenuates methamphetamine-induced disruptions in thermoregulation and activity in rats.
A methamphetamine vaccine attenuates methamphetamine-induced disruptions in thermoregulation and activity in rats.
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DOI：
10.1016/j.biopsych.2012.09.010
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发表时间：
2013-04-15
影响因子：
10.6
通讯作者：
Taffe, Michael A.
中科院分区：
文献类型：
--
作者：
Miller, Michelle L.;Moreno, Amira Y.;Aarde, Shawn M.;Creehan, Kevin M.;Vandewater, Sophia A.;Vaillancourt, Brittani D.;Wright, M. Jerry, Jr.;Janda, Kim D.;Taffe, Michael A.
目前还没有批准的治疗d-甲基苯丙胺(冰毒)成瘾的药物疗法，现有的疗法疗效有限。在使用免疫治疗方法治疗可卡因和尼古丁成瘾方面的进展激发了人们创造类似方法治疗冰毒成瘾的兴趣。这项研究调查了主动接种冰毒疫苗是否有可能在体内减弱对冰毒的反应。雄性SpragueDawley大鼠(N=32)接受了4次增强系列接种，其中包括3种候选抗冰毒疫苗(MH2(R)、MH6和MH7)中的1种或对照锁孔帽状血蓝蛋白结合疫苗(KLH)。测定了27℃环境温度下冰毒对直肠温度和车轮活动度的影响。然后，在随后的实验中(N=16)，将最有效的疫苗MH6与KLH进行对比，其中无线电遥测法在23°C的环境温度下测定家禽笼子的活动能力和体温。MH6疫苗产生了对冰毒具有纳摩尔亲和力的高抗体效价，并将冰毒隔离在大鼠的外围。在实验1中，MH6组阻断了27°C冰毒引起的体温调节和精神运动反应。在实验2中，在MH6组中，冰毒引起的体温下降和23°C下的运动活动也得到了缓解。实验2中的药代动力学研究表明，接种MH6疫苗的大鼠血清冰毒浓度高于对照组，但脑内冰毒浓度低于对照组，冰毒浓度与个体抗体效价相关。这些数据表明，主动免疫药物治疗对冰毒引起的生理和行为障碍提供了功能保护。
There are no approved pharmacotherapies for d-methamphetamine (METH) addiction and existing therapies have limited efficacy. Advances in using immunotherapeutic approaches for cocaine and nicotine addiction have stimulated interest in creating a similar approach for METH addiction. This study investigated whether active vaccination against METH could potentially attenuate responses to METH, in vivo. Male Sprague Dawley rats (N=32) received a 4-boost series with 1 of 3 candidate anti-METH vaccines (MH2(R), MH6, and MH7) or a control keyhole limpet hemocyanin conjugate vaccine (KLH). Effects of METH on rectal temperature and wheel activity at 27°C ambient temperature were determined. The most efficacious vaccine, MH6, was then contrasted with KLH in a subsequent experiment (N=16), wherein radiotelemetry determined home cage locomotor activity and body temperature at 23°C ambient temperature. The MH6 vaccine produced high antibody titers with nanomolar affinity for METH and sequestered METH in the periphery of rats. In Experiment 1, the thermoregulatory and psychomotor responses produced by METH at 27°C were blocked in the MH6 group. In Experiment 2, METH-induced decreases in body temperature and locomotor activity at 23°C were also attenuated in the MH6 group. A pharmacokinetic study in Experiment 2 showed that MH6-vaccinated rats had higher METH serum concentrations, yet lower brain METH concentrations than controls, and METH concentrations correlated with individual antibody titer. These data demonstrate that active immunopharmacotherapy provides functional protection against physiological and behavioral disruptions induced by METH.
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DOI：
10.4161/hv.5.4.7456
发表时间：
2009-04
期刊：
Human vaccines
影响因子：
--
作者：
Gentry WB;Rüedi-Bettschen D;Owens SM
通讯作者：
Owens SM
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：
0.3
作者：
Cerny, EH;Lévy, R;Cerny, T
通讯作者：
Cerny, T
影响因子：
4.5
作者：
Hendrickson, Howard;Laurenzana, Elizabeth;Owens, S. Michael
通讯作者：
Owens, S. Michael
DOI：
10.3109/00952990.2011.598592
发表时间：
2012-01
期刊：
The American journal of drug and alcohol abuse
影响因子：
--
作者：
Dallery J;Raiff B
通讯作者：
Raiff B