Effects of pregnancy on nicotine self-administration and nicotine pharmacokinetics in rats.
BACKGROUND
Because of the adverse effects of smoking during pregnancy, understanding the factors that influence maternal smoking may help in developing better treatments to help women quit smoking during pregnancy. Animal models could be useful for this purpose.


OBJECTIVE
The purpose of the present study was to begin the development of an animal model of smoking during pregnancy by initially characterizing nicotine self-administration (NSA) in pregnant rats. Another purpose was to begin to explore the effects of pregnancy on nicotine pharmacokinetics in rats.


METHODS
In experiment 1, female rats self-administering nicotine during 23-h sessions were examined throughout gestation and lactation. In experiment 2, locomotor activity was measured during pregnancy to assess further potential motor effects of pregnancy. Experiments 3 and 4 compared the single-dose pharmacokinetics of nicotine in male, nonpregnant female, and pregnant females in the first and third trimester of pregnancy and the first week of lactation.


RESULTS
NSA decreased over the course of pregnancy with NSA significantly lower in the third trimester compared to nonpregnant controls. NSA remained suppressed for up to 10 days into lactation. Locomotor behavior was also significantly suppressed during the second and third trimesters and throughout lactation. Nicotine elimination was slower in pregnant females compared to nonpregnant females only in the third trimester.


CONCLUSIONS
NSA, locomotor behavior, and nicotine elimination in rats are decreased during late pregnancy. The present study is the first to characterize NSA during pregnancy in animals, providing a potential model of maternal smoking in humans.
Lesage
Mark G
MG
Minneapolis Medical Research Foundation, 914 South 8th Street, D3-860, Minneapolis, MN 55404, USA. mlesage@mmrf.org
Keyler
Daniel E
DE
Burroughs
Danielle
D
Pentel
Paul R
PR
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D003216:Conditioning, Operant / Q000187:drug effects; D005260:Female; D007774:Lactation / Q000502:physiology; D008297:Male; D023421:Models, Animal; D009043:Motor Activity / Q000502:physiology; D009538:Nicotine / Q000493:pharmacokinetics* / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000493:pharmacokinetics* / Q000494:pharmacology; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012646:Self Administration; D012907:Smoking
D018722:Nicotinic Agonists; D009538:Nicotine