Kantak K M, Collins S L, Bond J, Fox B S
Department of Psychology, Boston University, MA 02215, USA.
Psychopharmacology (Berl). 2001 Jan;153(3):334-40. doi: 10.1007/s002130000555.
Following a 6-week immunization period consisting of three biweekly injections of the cocaine vaccine IPC-1010, the reacquisition of cocaine self-administration behavior in rats was previously shown to be reduced in a manner that was dependant on serum antibody level. The present studies were conducted to examine additional issues relevant to the clinical use of the vaccine.
One experiment was conducted to address the issue of whether exposure to cocaine during the immunization period would influence the ability of the vaccine to block cocaine self-administration. A second experiment was conducted to determine if the reductions in drug-seeking behavior and drug intake by the vaccine were behaviorally specific, or if behavior maintained by a non-drug reinforcer would be similarly affected.
Identical second-order schedules of cocaine (1 mg/kg) or food pellet (45 mg) delivery were used in rats. In both studies, the time course of changes in behavior during the 6-week immunization period was examined in vaccine and alum-treated control rats following baseline and extinction conditions.
The cocaine vaccine IPC-1010 induced average serum antibody levels of 0.07 mg/ml and significantly reduced self-administration behavior during the 2-week period following the third vaccine boost in a subgroup of rats with serum antibody levels greater than the average value. Cocaine self-administration behavior at this time point significantly correlated with serum antibody level. IPC-1010 did not alter responding maintained by food throughout the immunization period although serum antibody levels reached a similar average of 0.06 mg/ml in this group of rats.
These findings suggest that the reductions in drug-seeking behavior and drug intake after immunization with IPC-1010 did not result from a reduced ability of the rats to respond on the lever. Furthermore, daily exposure to cocaine during the immunization period did not influence the ability of the vaccine to reduce cocaine self-administration behavior that emerged gradually over time. These findings also confirm the need for a sufficiently high antibody level to blunt the reinforcing effects of cocaine.
在为期6周的免疫期内，每两周注射一次可卡因疫苗IPC - 1010，共注射三次。此前研究表明，大鼠可卡因自我给药行为的重新习得会以一种依赖血清抗体水平的方式减少。本研究旨在探讨与该疫苗临床应用相关的其他问题。
进行了一项实验，以解决免疫期接触可卡因是否会影响疫苗阻断可卡因自我给药能力的问题。进行了第二项实验，以确定疫苗导致的觅药行为和药物摄入量的减少是否具有行为特异性，或者由非药物强化物维持的行为是否会受到类似影响。
在大鼠中使用相同的二级可卡因（1毫克/千克）或食物颗粒（45毫克）给药方案。在两项研究中，在基线和消退条件后，对接受疫苗和明矾处理的对照大鼠在6周免疫期内的行为变化时间进程进行了检查。
可卡因疫苗IPC - 1010诱导的平均血清抗体水平为0.07毫克/毫升，在血清抗体水平高于平均值的一组大鼠中，第三次疫苗加强注射后的2周内，显著减少了自我给药行为。此时的可卡因自我给药行为与血清抗体水平显著相关。尽管该组大鼠的血清抗体水平达到了类似的平均0.06毫克/毫升，但在整个免疫期内，IPC - 1010并未改变由食物维持的反应。
这些发现表明，用IPC - 1010免疫后觅药行为和药物摄入量的减少并非由于大鼠按杠杆反应的能力降低所致。此外，免疫期内每日接触可卡因并未影响疫苗减少随时间逐渐出现的可卡因自我给药行为的能力。这些发现还证实了需要足够高的抗体水平来减弱可卡因的强化作用。
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