Chronic nicotine induces growth retardation in neonatal rat pups.
In the United State, 20% of pregnant women smoke. One of the most consistent adverse outcomes is reduced birth weight in the off-spring. Animal studies using chronic nicotine, the major psychoactive tobacco ingredient, have shown conflicting results, questioning the role of nicotine in growth retardation. To evaluate the direct effects of nicotine during a period equivalent to the human third trimester, we developed an oral gastric intubation model using neonatal rat pups. Nicotine (6 mg/kg/day) was dissolve in milk-formula and delivered during three feedings daily from postnatal day (P)1 to P7. Nicotine immediately and significantly [P<0.05] decreased weight gain per day (WGD) by 13.5% (+/-) 1 day after onset of treatment in both genders and throughout the treatment period. This resulted in significantly lower body weight at P4 and P5 in male and female pups, respectively. After nicotine withdrawal, WGD returned to control level within 1 day, whereas total body weight recovered by P18. There were no long-term consequences on body weight or growth pattern in either gender. The nicotinic acetylcholine receptor (nAChR) antagonist dihydro-beta-erythroidine (DHbetaE) reversed nicotine's effects on WGD suggesting an involvement of heteromeric alpha4beta2, whereas methyllycaconitine (MLA) an antagonist for the homomeric alpha7-type receptor was ineffective. The immediate decrease of growth in neonatal pups suggests that nicotine's effect on birth weight results from direct anorexic rather then indirect effects due to placental dysfunction or increased fetal hypoxia. The postnatal oral gastric intubation model seems to accurately reflect the direct effects of nicotine in neonates.
Huang
Luping Z
LZ
Department of Medical Pharmacology and Toxicology, College of Medicine, Texas A&M University System, Health Sciences Center, College Station, TX, USA.
Hsiao
Shu-Huei
SH
Trzeciakowski
Jerome
J
Frye
Gerald D
GD
Winzer-Serhan
Ursula H
UH
D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000254:growth & development; D004195:Disease Models, Animal; D005260:Female; D006130:Growth Disorders / Q000139:chemically induced*; D008297:Male; D009538:Nicotine / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics; D015430:Weight Gain / Q000187:drug effects
D009538:Nicotine