A nicotine conjugate vaccine reduces nicotine distribution to brain and attenuates its behavioral and cardiovascular effects in rats

Vaccination of animals to elicit drug-specific antibodies, or the passive t ransfer of such antibodies from other animals, can reduce the behavioral ef fects of drugs such as cocaine and heroin. To study the potential applicati on of this approach to treating nicotine dependence, IgG was isolated from rabbits immunized with a nicotine-protein conjugate vaccine. Anesthetized r ats received immune IgG containing nicotine-specific antibodies (Nic-IgG) o r control-IgG TV. Thirty minutes later, rats received nicotine at 0.03 mg/k g IV, equivalent on an mg/kg basis to the nicotine intake from two cigarett es by a smoker. Compared to control-IgG, Nic-IgG reduced the brain nicotine concentration in a dose-related manner (65% reduction at the highest IgG d ose). Pretreatment with Nic-IgG also reduced the distribution to brain of f ive repeated doses of nicotine (equivalent to the nicotine intake from 10 c igarettes) administered over 80 min. To study blood pressure effects, rats received control-IgG or Nic-IgG 1 day prior to administering nicotine. Nico tine-induced systolic blood pressure increases were attenuated by Nic-IgG i n a dose-related manner, and were almost completely blocked by the highest Nic-IgG dose. Pretreatment with Nic-IgG also completely prevented the nicot ine-induced stimulation of locomotor activity observed in rats receiving co ntrol-IgG. Nic-IgG did not prevent locomotor activation from cocaine, demon strating its specificity for nicotine. These data demonstrate that the admi nistration of nicotine-specific antibodies can reduce or prevent some of th e pharmacokinetic, cardiovascular, and behavioral consequences of nicotine in rats. Effects were observed at nicotine doses and nicotine serum concent rations equal to or exceeding those typically associated with nicotine expo sure in cigarette smokers. A potential role for immunization in the treatme nt of nicotine dependence is suggested. (C) 1999 Elsevier Science Inc.