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Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on February 11, 2003; DOI: 10.1124/jpet.102.046805

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Received for publication November 21, 2002.
Revised January 13, 2003.
Accepted for publication January 29, 2003.

Maternal vaccination against nicotine reduces nicotine distribution to fetal brain in rats

Dan E. Keyler 1, Donald Shoeman 2, Mark G. LeSage 3, Andrew D. Calvin 4, Paul R. Pentel 3*

1 College of Pharmacy, U. Minnesota, and Minneapolis Medical Research Foundation 2 Minneapolis Medical Research Foundation 3 U. Minnesota and Minneapolis Medical Research Foundation 4 School of Public Health, U. Minnesota

* Address correspondence to: E-mail: pente001{at}umn.edu

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 brain. The current study examined whether vaccination of female rats prior to 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 16-22. 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 prior to 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 prior to pregnancy, or passive immunization during pregnancy, can reduce the exposure of fetal brain to a single dose of maternally administered nicotine.


Key words: distribution, fetal, immunization, nicotine, tobacco, vaccine


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