Evaluation of anti-cocaine antibodies and a cocaine vaccine in a rat self-administration model
Evaluation of anti-cocaine antibodies and a cocaine vaccine in a rat self-administration model
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DOI：
10.1007/s002130050049
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发表时间：
2000-02-01
影响因子：
3.4
通讯作者：
Fox, BS
中科院分区：
文献类型：
--
作者：
Kantak, KN;Collins, SL;Fox, BS
理由：以前的抗可卡因单克隆抗体临床前研究对评估疫苗改变可卡因自我给药行为的有效性留下了几个关键问题。目的：本研究的目的是确定，首先，自我给药行为的改变是否与抗体水平有系统的关系，其次，抗体如何影响不同剂量可卡因的自我给药。方法：采用大鼠给药二级计划进行两项实验。第一个是使用抗可卡因单克隆抗体MO240的被动给药研究，以检查抗体水平与可卡因自我给药行为之间的关系；第二个是主动免疫研究，以检查可卡因疫苗IPC-1010阻断各种剂量可卡因自我给药的功效。结果：对照和4 mg、12 mg MO240被动给药实验表明，1 mg/kg可卡因训练剂量的拮抗作用依赖于抗体水平。在血清抗体水平持续高于0.05 mg/ml的动物中，有足够的抗体量可以减少觅药行为和药物摄入。在主动免疫实验中，可卡因疫苗IPC-1010诱导的平均血清抗体水平为0.08 mg/ml，减少了1 mg/kg可卡因的行为再获得。免疫后可卡因自我给药的拮抗作用在可卡因剂量范围内都很明显，仅在血清抗体水平超过0.05 mg/ml的动物中才明显。此外，没有证据表明在所检测的剂量范围内（高达5.6 mg/kg），拮抗作用是可以克服的。结论：只要抗体水平有足够的浓度，可卡因疫苗免疫后在一定剂量范围内的可卡因自我给药拮抗是可行的。
Rationale: Previous pre-clinical studies with an anti-cocaine monoclonal antibody left open several issues critical to assessing the effectiveness of a vaccine for altering cocaine self-administration behavior. Objectives: The objectives of this study were to determine, first, whether changes in self-administration behavior would be systematically related to antibody level and, second, how the antibody affected the self-administration of different doses of cocaine. Methods: Two experiments were conducted using a second-order schedule of drug delivery in rats. The first was a passive-administration study using the anti-cocaine monoclonal antibody MO240 to examine the relationship between antibody level and cocaine self-administration behavior, and the second was an active-immunization study to examine the efficacy of the cocaine vaccine IPC-1010 for blocking various doses of self-administered cocaine. Results: The passive-administration experiment with control and 4-mg or 12-mg MO240 treatments showed that antagonism of the 1 mg/kg cocaine training dose was dependent on antibody level. In animals whose serum antibody levels were sustained above 0.05 mg/ml, there was a sufficient amount of antibody to reduce drug-seeking behavior and drug intake. In the active-immunization experiment, the cocaine vaccine IPC-1010 induced average serum antibody levels of 0.08 mg/ml and reduced the reacquisition of behavior by 1 mg/kg cocaine. Antagonism of cocaine self-administration after immunization was evident across a range of doses of cocaine and was only apparent in animals whose serum antibody levels exceeded 0.05 mg/ml. Furthermore, there was no evidence that the antagonism was surmountable within the dose range examined (up to 5.6 mg/kg). Conclusions: Antagonism of cocaine self-administration across a range of doses is feasible after immunization with a cocaine vaccine as long as antibody levels are of a sufficient concentration.