A vaccine against methamphetamine attenuates its behavioral effects in mice.
A vaccine against methamphetamine attenuates its behavioral effects in mice.
复制标题
DOI：
10.1016/j.drugalcdep.2012.09.007
复制
发表时间：
2013-04-01
影响因子：
4.2
通讯作者：
Orson, Frank M.
中科院分区：
文献类型：
--
作者：
Shen, Xiaoyun Y.;Kosten, Therese A.;Lopez, Angel Y.;Kinsey, Berma M.;Kosten, Thomas R.;Orson, Frank M.
关键词：
疫苗具有治疗甲基苯丙胺 (MA) 成瘾的潜力。我们测试了针对 MA（琥珀酰甲基苯丙胺-匙孔血蓝蛋白载体蛋白；SMA-KLH）的结合疫苗是否会产生 MA 抗体并改变 MA 诱导的行为。小鼠被注射 SMA-KLH，并在 3 周和 20 周后接受加强注射。血清抗体滴度在 4-6 周时达到峰值水平，在 18 周内保持在适度水平，在第二次加强后 22 周再次达到峰值，并在 35 周时仍然升高。 7 周时，接种疫苗和未接种疫苗的小鼠组被注射三种 MA 剂量（1、2 或 3 mg/kg）中的一种，以评估运动活性。未接种疫苗的小鼠表现出 MA 的剂量依赖性效应，在最低剂量时出现运动减退，在最高剂量时出现活动水平升高。 SMA-KLH 组中两种剂量效应均降低，尤其是 MA 给药后后期低剂量引起的运动不足。 30周后，分别对接种疫苗和未接种疫苗的小鼠进行MA场所条件训练，使用0（媒介物）或0.5 mg/kg MA。尽管在测试组与基线组之间花费在 MA 配对侧的时间没有差异，但与对照组相比，用 MA 调节的 SMA-KLH 小鼠表现出减少的条件接近行为和降低的条件活动水平。这些数据表明 SMA-KLH 减弱了 MA 支持位置调节的能力，并减少或延迟了其运动效应。总体而言，结果支持 SMA-KLH 作为候选 MA 疫苗。
Vaccines have treatment potential for methamphetamine (MA) addiction. We tested whether a conjugate vaccine against MA (succinyl-methamphetamine–keyhole limpet hemocyanin carrier protein; SMA-KLH) would generate MA antibodies and alter MA-induced behaviors. Mice were injected with SMA-KLH and received booster administrations 3-and 20-weeks later. Serum antibody titers reached peak levels by 4–6 weeks, remained at a modest level through 18-weeks, peaked again at 22-wks after the second boost, and were still elevated at 35-weeks. At 7 weeks, groups of vaccinated and non-vaccinated mice were administered one of three MA doses (1, 2, or 3 mg/kg) to assess locomotor activity. Non-vaccinated mice showed dose-dependent effects of MA with hypolocomotion at the lowest dose and elevated activity levels at the highest dose. Both dose effects were reduced in SMA-KLH groups, particularly low dose-induced hypolocomotion at later times post MA administration. Separate groups of vaccinated and non-vaccinated mice were trained in MA place conditioning at 30-weeks with either 0 (vehicle) or 0.5 mg/kg MA. Although times spent in the MA-paired side did not differ between groups on Test vs. Baseline sessions, SMA-KLH mice conditioned with MA showed reduced conditioned approach behaviors and decreased conditioned activity levels compared to control groups. These data suggest SMA-KLH attenuates the ability of MA to support place conditioning and reduces or delays its locomotor effects. Overall, results support SMA-KLH as a candidate MA vaccine.
登录
查看更多内容
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：
8.2
作者：
Antoniou, K;Kafetzopoulos, E;Marselos, M
通讯作者：
Marselos, M
影响因子：
5.5
作者：
Duryee, Michael J.;Bevins, Rick A.;Sanderson, Sam D.
通讯作者：
Sanderson, Sam D.
影响因子：
5
作者：
ELLINWOOD, EH;BALSTER, RL
通讯作者：
BALSTER, RL
影响因子：
6.7
作者：
Hatsukami, DK;Rennard, S;Pentel, PR
通讯作者：
Pentel, PR