Vaccination against nicotine does not prevent nicotine-induced changes in fetal nicotinic receptor binding and c-fos mRNA expression in rats.
Gestational exposure of rats to nicotine produces long-lasting alterations in brain development. Vaccination of adult female rats against nicotine reduces the distribution of maternally administered nicotine to fetal brain, suggesting that vaccination might protect against these effects. In the current study, the effects of vaccination on nicotine-induced changes in fetal (3)H-epibatidine binding and c-fos mRNA expression were evaluated using tissue from a previous pharmacokinetic study of vaccination. An intermittent nicotine dosing regimen designed to resemble nicotine intake in a smoker was administered from GD1-20. Peak nicotine levels in fetal brain were reduced by vaccination, whereas the chronic accumulation of nicotine in fetal brain was not. Gestational nicotine exposure produced significant increases in (125)I-epibatidine binding to brain and spinal cord on GD20, and decreased c-fos mRNA expression in fetal striatum, adrenal and lung. Vaccination did not significantly alter these effects. These data suggest that nicotine dosing, using a clinically relevant intermittent bolus dose regimen, produces substantial changes in fetal nicotinic receptor and c-fos mRNA expression. The decrease in c-fos mRNA expression contrasts with previously reported increases, and suggests that the nicotine dosing regimen used may influence its effects. The lack of effect of vaccination suggests that the cumulative exposure of fetal tissues to nicotine may influence the measured parameters to a greater extent than peak exposure levels.
Pentel
P R
PR
Department of Medicine, University of Minnesota Medical School, Minneapolis, MN, USA. pentel@umn.edu
Keyler
D E
DE
Chen
Y
Y
LeSage
M G
MG
Dufek
M B
MB
Le
C
C
Leslie
F M
FM
D000704:Analysis of Variance; D000818:Animals; D001345:Autoradiography / Q000379:methods; D001921:Brain / Q000187:drug effects; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000493:pharmacokinetics; D004622:Embryo, Mammalian; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology*; D009538:Nicotine / Q000276:immunology* / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000493:pharmacokinetics; D011247:Pregnancy; D011485:Protein Binding / Q000187:drug effects; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism*; D011725:Pyridines / Q000493:pharmacokinetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism*; D014316:Tritium / Q000493:pharmacokinetics; D014611:Vaccination
D019086:Bridged Bicyclo Compounds, Heterocyclic; D018722:Nicotinic Agonists; D016760:Proto-Oncogene Proteins c-fos; D011725:Pyridines; D012333:RNA, Messenger; D011978:Receptors, Nicotinic; D014316:Tritium; D009538:Nicotine; C082748:epibatidine