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Vaccination against nicotine during continued nicotine
administration in rats: immunogenicity of the vaccine and effects on
nicotine distribution to brain.
Hieda Y, Keyler DE, Ennifar S, Fattom A, Pentel PR
[Medline record in process]
Vaccination against nicotine has been proposed as a potential treatment for
nicotine dependence. Because vaccination may take months to elicit
satisfactory antibody levels, the clinical usefulness of this approach will
be enhanced if vaccination can be accomplished during continued nicotine
intake (e.g., before a smoker quits). The current study examined the
immunogenicity of a nicotine conjugate vaccine during continued nicotine
dosing in rats, and its effects on nicotine distribution to brain. In the
first experiment, nicotine was administered over 11 weeks as 20 intra venous
(i.v.) bolus injections per day during the rat's active cycle to simulate
the usual pattern of nicotine intake from cigarette smoking. In the second
experiment, rats received a continuous s.c. infusion of nicotine by osmotic
pump for 11 weeks to provide serum nicotine concentrations equivalent to
those of a heavy smoker and 24 h/day nicotine exposure. Nicotine-specific
antibody titers after the third booster dose were not compromised by either
regimen of concurrent nicotine administration compared to those of rats
receiving saline. A single additional i.v. nicotine dose was administered at
the end of each experiment. The distribution of this single nicotine dose to
brain was reduced by 40-60% in vaccinated rats compared to controls. Vaccine
efficacy in reducing nicotine distribution to brain was not compromised by
concurrent nicotine administration. These data suggest that vaccination
during concurrent nicotine administration is feasible, and that the ability
of vaccination to reduce nicotine distribution to brain is preserved even
after months of nicotine dosing at rates approximating cigarette smoking.
PMID: 10963853, UI: 20420003
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