Carrera M Rocío A, Ashley Jon A, Hoffman Timothy Z, Isomura Shigeki, Wirsching Peter, Koob George F, Janda Kim D
Department of Chemistry, The Scripps Research Institute and the Skaggs Institute for Chemical Biology, 10550N. Torrey Pines Road, La Jolla, CA 92037, USA.
Bioorg Med Chem. 2004 Feb 1;12(3):563-70. doi: 10.1016/j.bmc.2003.11.029.
Despite the enormous health risks, people continue to smoke and use tobacco primarily as a result of nicotine addiction. As part of our immunopharmacotherapy research, the effects of active and passive immunizations on acute nicotine-induced locomotor activity in rats were investigated. To this end, rats were immunized with either a NIC-KLH immunoconjugate vaccine designed to elicit an antinicotine immune response, or were administered an antinicotine monoclonal antibody, NIC9D9, prior to a series of nicotine challenges and testing sessions. Vaccinated rats showed a 45% decrease in locomotor activity compared to a 16% decrease in controls. Passive immunization with NIC9D9 resulted in a 66.9% decrease in locomotor activity versus a 3.4% decrease in controls. Consistent with the behavioral data, much less nicotine was found in the brains of immunized rats. The results support the potential clinical value of immunopharmacotherapy for nicotine addiction in the context of tobacco cessation programs.
尽管存在巨大的健康风险，但人们仍继续吸烟和使用烟草，主要是由于尼古丁成瘾。作为我们免疫药物治疗研究的一部分，我们研究了主动免疫和被动免疫对大鼠急性尼古丁诱导的运动活动的影响。为此，在一系列尼古丁激发和测试之前，给大鼠接种旨在引发抗尼古丁免疫反应的NIC-KLH免疫缀合物疫苗，或给予抗尼古丁单克隆抗体NIC9D9。与对照组下降16%相比，接种疫苗的大鼠运动活动下降了45%。用NIC9D9进行被动免疫导致运动活动下降66.9%，而对照组下降3.4%。与行为数据一致，在免疫大鼠的大脑中发现的尼古丁要少得多。这些结果支持了免疫药物治疗在戒烟计划中对尼古丁成瘾的潜在临床价值。
