Nicotine Vaccine & Nicotine Occupancy of Brain Nicotinic Receptors

描述（由申请人提供）：在过去的三十年中，成瘾领域一直非常关注用于预防和治疗吸烟（尼古丁依赖）的疫苗的开发。基于啮齿动物的临床前研究，推测的作用机制是疫苗接种产生的抗体与尼古丁结合，降低尼古丁穿过血脑屏障并占据中皮质边缘奖赏通路中的烟碱乙酰胆碱受体（nAChR）的速率和量。在本研究中，我们建议在活体吸烟者中验证这种机制。具体而言，我们将使用烟碱激动剂[123 I]5 IA 85380（[123 I]5 IA）和单光子发射计算机断层扫描（SPECT）对大脑22 nAChR进行成像，以确定吸烟者在接种NicVax疫苗前后接受IV尼古丁激发后大脑22 nAChR的尼古丁占用量。我们假设接种疫苗后，尼古丁占据22 nAChR的量将减少至少50%。如果得到证实，这种尼古丁占据nAChR的量的减少将解释为什么接种疫苗的人在吸烟时不太可能上瘾，而目前的吸烟者不会从吸烟中获得同样的满足感。

DESCRIPTION (provided by applicant): Over the past three decades there has been a strong focus in the field of addiction towards the development of vaccines for the prevention and treatment of tobacco smoking (nicotine dependence). Based on preclinical studies in rodents, the presumed mechanism of action is that the antibodies produced by vaccination, bind to nicotine and decrease the rate and the amount of nicotine that is able to cross the blood brain barrier and occupy nicotinic acetylcholine receptors (nAChR) in the mesocorticolimbic reward pathway. In the present study, we propose to validate this mechanism in living human smokers. Specifically, we will image brain 22 nAChR using the nicotinic agonist [123I]5 IA 85380 ([123I]5 IA) and single photon emission computed tomography (SPECT) to determine the amount of nicotine occupancy of brain 22 nAChR after an IV nicotine challenge in smokers before and after vaccination with the NicVax vaccine. We hypothesize that after vaccination, the amount of nicotine occupying 22 nAChR will be reduced by at least 50%. If confirmed, this reduction in the amount of nicotine occupying nAChR will explain why, vaccinated individuals will be less likely to become addicted if they smoke, and current smokers will not experience the same satisfaction from smoking.