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Research ArticleABSORPTION, DISTRIBUTION, METABOLISM, AND EXCRETION

Maternal Vaccination Against Nicotine Reduces Nicotine Distribution to Fetal Brain in Rats

D. E. Keyler, D. Shoeman, M. G. LeSage, A. D. Calvin and P. R. Pentel
Journal of Pharmacology and Experimental Therapeutics May 2003, 305 (2) 587-592; DOI: https://doi.org/10.1124/jpet.102.046805
D. E. Keyler
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D. Shoeman
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M. G. LeSage
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A. D. Calvin
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P. R. Pentel
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Abstract

Cigarette smoking during pregnancy is associated with a variety of adverse fetal outcomes. Nicotine is a likely contributor to these adverse effects, with fetal brain as one target organ. Vaccination of adult male rats against nicotine has been shown to reduce nicotine distribution to the brain. The current study examined whether vaccination of female rats before pregnancy would reduce the distribution to fetal brain of a single nicotine dose administered during gestation. Female rats immunized with a nicotine conjugate vaccine received a single dose of nicotine 0.03 mg/kg i.v. on gestational day 16 to 22. Five minutes later, vaccinated rats had substantially higher bound and lower unbound serum nicotine concentration and lower brain nicotine concentration than controls. Fetal brain nicotine concentration was reduced by 43% in vaccinated rats, comparable to the reduction in the maternal brain nicotine concentration. The whole-fetus nicotine concentration was not altered by vaccination. A similar experiment was performed in which pregnant rats were passively immunized with rabbit nicotine-specific IgG 7 or 21 mg/kg just before nicotine dosing. The effects of passive immunization on nicotine distribution in the mother were IgG dose-related and the higher dose reduced nicotine distribution to fetal brain by 60%. These data suggest that vaccine effects on nicotine distribution to serum and brain are similar in pregnant female rats to those previously reported in adult males. Vaccination of female rats before pregnancy, or passive immunization during pregnancy, can reduce the exposure of fetal brain to a single dose of maternally administered nicotine.

Footnotes

  • Supported by National Institutes of Health Grants P50-DA13333 and DA10714.

  • DOI: 10.1124/jpet.102.046805

  • Abbreviations:
    Nic-IgG
    nicotine-specific IgG
    ELISA
    enzyme-linked immunosorbent assay
    ANOVA
    analysis of variance
    • Received November 20, 2002.
    • Accepted January 29, 2003.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 305 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 305, Issue 2
1 May 2003
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Research ArticleABSORPTION, DISTRIBUTION, METABOLISM, AND EXCRETION

Maternal Vaccination Against Nicotine Reduces Nicotine Distribution to Fetal Brain in Rats

D. E. Keyler, D. Shoeman, M. G. LeSage, A. D. Calvin and P. R. Pentel
Journal of Pharmacology and Experimental Therapeutics May 1, 2003, 305 (2) 587-592; DOI: https://doi.org/10.1124/jpet.102.046805

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Research ArticleABSORPTION, DISTRIBUTION, METABOLISM, AND EXCRETION

Maternal Vaccination Against Nicotine Reduces Nicotine Distribution to Fetal Brain in Rats

D. E. Keyler, D. Shoeman, M. G. LeSage, A. D. Calvin and P. R. Pentel
Journal of Pharmacology and Experimental Therapeutics May 1, 2003, 305 (2) 587-592; DOI: https://doi.org/10.1124/jpet.102.046805
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