title: Passive immunization with a nicotine-specific monoclonal antibody decreases brain nicotine levels but does not precipitate withdrawal in nicotine-dependent rats.
abstract: Vaccination against nicotine is under investigation as a treatment for tobacco dependence. Passive immunization with nicotine-specific antibodies represents a complementary strategy to vaccination. A potential adverse effect of passive immunization in nicotine-dependent individuals is that it may lead to a rapid reduction in brain nicotine levels and trigger withdrawal. The goal of this study was to determine if passive immunization with the nicotine-specific monoclonal antibody Nic311 precipitated withdrawal in nicotine-dependent rats as measured by increases in brain reward thresholds and somatic signs. Another cohort of rats was used to measure brain nicotine levels after Nic311 administration. Nic311 30, 80 or 240 mg/kg reduced brain nicotine concentrations by 45, 83 or 92% compared to controls. None of these Nic311 doses precipitated withdrawal measured at intervals up to 72 h following antibody administration. Administration of the nicotinic antagonist mecamylamine precipitated a robust nicotine withdrawal syndrome. Therefore, a substantial, but not complete, acute reduction in brain nicotine levels following passive immunization was not sufficient to precipitate nicotine withdrawal in nicotine-dependent rats. The Nic311 doses used have been shown to attenuate the behavioral effects of nicotine, suggesting that the use of passive immunization to treat nicotine addiction is not likely to precipitate withdrawal.
authors.affiliation: Minneapolis Medical Research Foundation, Minneapolis, MN 55404, USA.
authors.forename: Samuel A
authors.initials: SA
authors.lastname: Roiko
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Harris
authors.forename: Mark G
authors.initials: MG
authors.lastname: LeSage
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Keyler
authors.forename: Paul R
authors.initials: PR
authors.lastname: Pentel
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D007116:Immunization, Passive; D007074:Immunoglobulin G / Q000378:metabolism; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D009538:Nicotine / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism*; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012201:Reward; D012653:Self Stimulation; D013238:Stereotaxic Techniques; D013375:Substance Withdrawal Syndrome / Q000523:psychology*; D014029:Tobacco Use Disorder / Q000523:psychology*
chemical_list: D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D008464:Mecamylamine; D009538:Nicotine