Cited by 33Smoking Behavior and CessationMonoclonal and Polyclonal Antibodies ResearchNicotinic Acetylcholine Receptors Study

Vaccination against nicotine alters the distribution of nicotine delivered via cigarette smoke inhalation to rats

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Pravetoni, M., Keyler, D.E., Raleigh, M.D., Harris, A.C., LeSage, M.G., Mattson, C.K., Pettersson, S., Pentel, P.R.·2011·Biochemical Pharmacology

Abstract

Preclinical models of nicotine vaccine pharmacology have relied on i.v. or s.c. administration of nicotine. Models using cigarette smoke inhalation might more accurately simulate nicotine exposure in smokers. Nicotine vaccine effects were examined in rats using two cigarette smoke exposure models: a 10 min nose-only exposure (NSE) producing serum nicotine levels equivalent to the nicotine boost from 1 cigarette in a smoker, and a 2h whole-body exposure (WBE) producing serum nicotine levels similar to those associated with regular mid-day smoking. Vaccination prior to 10min smoke NSE reduced nicotine distribution to brain by 90%, comparable to its effect on nicotine administered i.v. Vaccination prior to 2 h smoke WBE reduced nicotine distribution to brain by 35%. The nicotine concentration in broncheoalveolar lavage (BAL) fluid obtained after 2 h WBE was increased by 230% in vaccinated rats but was also increased in rats passively immunized with a nicotine-specific monoclonal antibody, and so was likely due to transfer of antibody from serum rather than local production at the pulmonary mucosa. Nicotine-specific IgA was not detectable in BAL fluid, but titers in serum were appreciable at 21-25% of the IgG titer and could contribute to vaccine efficacy. Both vaccination and passive immunization are effective in reducing nicotine distribution to brain in rats when nicotine is delivered via inhaled cigarette smoke. These data validate results previously obtained in rodents for nicotine vaccines using i.v. or s.c. nicotine dosing and provide a quantitative method for studying aspects of nicotine exposure which are unique to cigarette smoke inhalation.

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Crossref · 10.1016/j.bcp.2011.02.004

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  1. [30]Rose JE Behm FM Westman EC Coleman RE Arterial nicotine kinetics during cigarette smoking and intravenous nicotine administration: implications for addiction Drug Alcohol Depend 1999 56 99 107 10482401

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Authors
Pravetoni, M., Keyler, D. E., Raleigh, M. D., Harris, A. C., LeSage, M. G., Mattson, C. K., Pettersson, S., & Pentel, P. R.
Affiliations
University of Minnesota (US)
Corresponding author
Pentel, P.R.
Venue
Biochemical Pharmacology
Publisher
Elsevier BV
Published
2011-05
Volume
81
Issue
9
Pages
1164-1170
ISSN
0006-2952 (ISSN-L)
OpenAlex
W2014155249
Cited by
33
References
45
Citations by year
2025: 1 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 3 · 2018: 2 · 2017: 1 · 2016: 2 · 2015: 3 · 2014: 3 · 2013: 5 · 2012: 9
FWCI
3.93
Type
journal article
Language
en
Open access
Locations
  • Biochemical Pharmacology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute on Drug Abuse (T32-DA-07097, R01DA010714, DA10714, DA010714-13S1, T32DA007097)
Topics
  • Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
Keywords
nicotine vaccine, cigarette smoke inhalation, passive immunization, bronchoalveolar lavage, smoking cessation, nicotine pharmacokinetics
MeSH terms
Administration, Inhalation, Animals, Enzyme-Linked Immunosorbent Assay, Male, Nicotine, Smoke, Nicotiana, Vaccines, Rats, Sprague-Dawley, Rats

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