PMID- 15826609
OWN - NLM
STAT- MEDLINE
DCOM- 20050524
LR  - 20151119
IS  - 0006-2952 (Print)
IS  - 0006-2952 (Linking)
VI  - 69
IP  - 9
DP  - 2005 May 1
TI  - Reduced nicotine distribution from mother to fetal brain in rats vaccinated 
      against nicotine: time course and influence of nicotine dosing regimen.
PG  - 1385-95
AB  - Nicotine is a teratogen in rats and possibly in humans. Vaccination against 
      nicotine is being studied as a possible treatment for nicotine dependence. The 
      safety of maternal vaccination against nicotine during or prior to pregnancy is 
      not known. In this study, female rats were vaccinated and then administered acute 
      or chronic nicotine during pregnancy at doses simulating nicotine exposure in 
      smokers. Maternal vaccination reduced nicotine distribution to both maternal 
      brain (44-47%) and fetal brain (17-39%) for up to 25 min after a single maternal 
      nicotine dose administered on gestational day (GD) 20, but had a smaller effect 
      on nicotine distribution to brain after continuous nicotine infusion. Nicotine 
      distribution to maternal or fetal brain after repeated nicotine bolus doses was 
      reduced immediately following an individual dose in vaccinated rats, but the 
      chronic accumulation of nicotine in fetal brain was not altered. Nicotine 
      distribution to whole fetus, in contrast to fetal brain, was generally not 
      altered by vaccination. Nicotine-specific antibody concentration in fetal serum 
      was 10% that of maternal serum, and in fetal brain was <1% of maternal serum. 
      Although nicotine transfer to the whole fetus was not reduced by vaccination, 
      protein binding data suggest that nicotine-specific antibody transferred from 
      mother to fetus served to bind nicotine in fetal serum, reduce the unbound 
      nicotine concentration, and thereby reduce nicotine distribution to fetal brain. 
      These data comment on the safety of vaccination against nicotine during 
      pregnancy, and suggest that vaccination may reduce the distribution of nicotine 
      to fetal brain under some nicotine dosing conditions.
FAU - Keyler, Daniel E
AU  - Keyler DE
AD  - Minneapolis Medical Research Foundation, Hennepin County Medical Center, 
      Minneapolis, MN 55415, USA.
FAU - Dufek, Matthew B
AU  - Dufek MB
FAU - Calvin, Andrew D
AU  - Calvin AD
FAU - Bramwell, Thomas J
AU  - Bramwell TJ
FAU - LeSage, Mark G
AU  - LeSage MG
FAU - Raphael, Donna E
AU  - Raphael DE
FAU - Ross, Cathy A
AU  - Ross CA
FAU - Le, Chap T
AU  - Le CT
FAU - Pentel, Paul R
AU  - Pentel PR
LA  - eng
GR  - DA 10714/DA/NIDA NIH HHS/United States
GR  - DA 15668/DA/NIDA NIH HHS/United States
GR  - P50 DA 13333/DA/NIDA NIH HHS/United States
GR  - P50 HL 61193/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (Nicotinic Agonists)
RN  - 0 (Vaccines, Conjugate)
RN  - 6M3C89ZY6R (Nicotine)
SB  - IM
MH  - Animals
MH  - Brain/drug effects/*metabolism
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Fetus
MH  - Maternal-Fetal Exchange
MH  - Nicotine/*immunology/*pharmacokinetics
MH  - Nicotinic Agonists/*immunology/*pharmacology
MH  - Pregnancy
MH  - Protein Binding
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Time Factors
MH  - Tissue Distribution
MH  - *Vaccination
MH  - Vaccines, Conjugate/administration & dosage/immunology
EDAT- 2005/04/14 09:00
MHDA- 2005/05/25 09:00
CRDT- 2005/04/14 09:00
PHST- 2004/11/22 00:00 [received]
PHST- 2005/02/02 00:00 [accepted]
PHST- 2005/04/14 09:00 [pubmed]
PHST- 2005/05/25 09:00 [medline]
PHST- 2005/04/14 09:00 [entrez]
AID - S0006-2952(05)00094-8 [pii]
AID - 10.1016/j.bcp.2005.02.007 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 2005 May 1;69(9):1385-95. doi: 10.1016/j.bcp.2005.02.007.