? Cigarette smoking prevails as the largest preventable risk factor for mortality in developed countries. Smokers procure their habit in order to maintain nicotine levels in the brain, where it exerts its powerfully addictive effects. Nicotine-replacement therapy, the most widely used treatment for nicotine dependence, has only been modestly successful. Immunopharmacotherapy offers an alternate venue, whereby the passage of nicotine into the brain is blocked by peripherally circulating anti-nicotine antibodies, thereby circumventing central pharmacological interventions. In laboratory animals, nicotine induces two main behavioral correlates: a distinct, biphasic pattern of psychomotor induction, and the self-administration of the drug due to its positive reinforcing properties. In order to explore the efficacy of passive immunization against the psychoactive and rewarding effects of nicotine in the rat, a comprehensive psychopharmacological assessment using various animal behavioral paradigms is proposed. First, the efficacy of the anti-nicotine monoclonal antibody NIC9D9 in blocking the psychomotor effects of nicotine will be tested using an animal model of locomotor activity. Second, a nicotine self-administration dose-response assay will be employed to study the effects of NIC9D9 on the reinforcing properties of nicotine. Lastly, in the effort to address the grave problem of relapse among cigarette smokers, an extensive study using a well-established animal model of nicotine self-administration reinstatement will be conducted. Together, the proposed studies will provide important insight into the potential benefits of immunopharmacotherapy against nicotine addiction. ? ? ? ?
| Carrera, M Rocio A; Meijler, Michael M; Janda, Kim D (2004) Cocaine pharmacology and current pharmacotherapies for its abuse. Bioorg Med Chem 12:5019-30 |
