Effects of a methamphetamine vaccine, IXT-v100, on methamphetamine-related behaviors
Effects of a methamphetamine vaccine, IXT-v100, on methamphetamine-related behaviors
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DOI：
10.1007/s00213-019-05399-6
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发表时间：
2019-11-22
影响因子：
3.4
通讯作者：
Goeder, Nicholas E. s
中科院分区：
文献类型：
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作者：
Keller, Courtney M.;Spence, Allyson L.;Goeder, Nicholas E. s
理由：疫苗已被开发为甲基苯丙胺（冰毒）使用障碍（MUD）的潜在治疗方法。用甲氨蝶呤疫苗IXT-v100进行免疫接种先前已显示出引发对甲氨蝶呤具有高亲和力的抗体，因此可能是MUD的有效治疗。目的：这些研究旨在确定IXT-v100对大鼠吸食和觅药行为的疗效。研究方法：在获得和维持研究中，训练雄性和雌性大鼠在接种疫苗后8周内自我施用甲基苯丙胺（0.06 mg/kg/输注）。在过去的4周里，冰毒的剂量每周增加或减少。为了评估寻求冰毒的行为，使用了冰毒引发的反应模型。训练大鼠自我施用冰毒5周，然后是5周或11周的强制禁欲期，在此期间动物接种疫苗。然后，在用甲基苯丙胺（lmg/kg，i. p.）但在治疗过程中没有服用冰毒反应被记录下来，并作为一个衡量冰毒寻求。结果如下：来自Wistar大鼠中的获得和维持研究的结果显示，用含有吡喃葡萄糖基脂质A稳定乳剂的IXT-v100佐剂接种降低了将自我施用中等水平甲氧苯丙胺的动物的百分比。在甲基引发的反应性研究中，来自男性的结果表明，接种疫苗显着减弱了寻找甲基的行为。结论：总之，这些结果表明，接种IXT-v100疫苗可能有效减少患有MUD的人的甲基摄入和甲基寻求行为。
Rationale: Vaccines have been developed as a potential treatment for methamphetamine (meth) use disorder (MUD). Immunization with the meth vaccine IXT-v100 has previously been shown to elicit antibodies with high affinity for meth and thus may be an effective treatment for MUD. Objectives: These studies were designed to determine the efficacy of IXT-v100 on meth-taking and meth-seeking behaviors in rats. Methods: In the acquisition and maintenance study, male and female rats were trained to self-administer meth (0.06 mg/kg/infusion) over an 8-week period following vaccination. In the last 4 weeks, the dose of meth was increased or decreased each week. To assess meth-seeking behavior, the meth-primed reactivity model was used. Rats were trained to self-administer meth for 5 weeks, followed by a 5-week or 11-week forced abstinence period during which the animals were vaccinated. Rats were then placed back into the self-administration chamber immediately after being injected with meth (1 mg/kg, i.p.) but did not receive meth during the session. Responses were recorded and used as a measure of meth seeking. Results: Results from the acquisition and maintenance study in Wistar rats show that vaccination with IXT-v100 adjuvanted with glucopyranosyl lipid A stable emulsion decreases the percentage of animals that will self-administer a moderate level of meth. In the meth-primed reactivity studies, results from males showed that vaccination significantly attenuates meth-seeking behavior. Conclusion: Together, these results suggest vaccination with IXT-v100 may be effective at decreasing meth-taking and meth-seeking behaviors in humans suffering with MUD.