Chronic nicotine induces growth retardation in neonatal rat pups

Huang, Luping Z.; Hsiao, Sigmund; Trzeciakowski, Jerome P.; Frye, Gerald D.; Winzer‐Serhan, Ursula H.

doi:10.1016/j.lfs.2005.07.047

Cited by 32 publications

(34 citation statements)

References 78 publications

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“…The finding of reduced birth weight in nicotine-treated animals is in agreement with previous studies (Bamford and Carroll, 1999;Gauda et al, 2001;Simakajornboon et al, 2004). Recent studies suggested that decreased birth weight from maternal nicotine exposure resulted from direct effects of nicotine rather than indirect effects due to placental insufficiency or fetal hypoxia (Huang et al, 2006). Nicotine crosses the placenta with fetal blood levels 15% greater than those of the mother (Lambers and Clark, 1996).…”

Section: Discussionsupporting

confidence: 90%

Fetal and Neonatal Nicotine Exposure Differentially Regulates Vascular Contractility in Adult Male and Female Offspring

Xiao¹,

Huang²,

Lawrence³

et al. 2006

J Pharmacol Exp Ther

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Epidemiologic studies suggest that prenatal exposure to maternal cigarette smoking is associated with an increased risk of elevated blood pressure in postnatal life. The present study was designed to test the hypothesis that fetal and neonatal nicotine exposure increased vascular contractility in adult offspring. Nicotine was administered to pregnant rats via s.c. osmotic minipumps throughout gestation and up to 10 days after delivery. Aortas were isolated from adult male and female offspring at the age of 3 months old. Nicotine significantly increased KCland norepinephrine-induced contractions of the aorta in male, but not female, offspring. Inhibition of endothelial nitric oxide synthase (eNOS) with N G -nitro-L-arginine (L-NNA) significantly increased norepinephrine-induced contractions in control male offspring but showed no effect in nicotine-treated male offspring. In the presence of L-NNA, there was no significant difference in norepinephrine-induced contractions between control and nicotine-treated males. In contrast, nicotine caused a significant increase in L-NNA-mediated potentiation of norepinephrine-induced contractions in female offspring. Nicotine had no effect on sodium nitroprusside-induced endotheliumindependent relaxations of aortas from either male or female offspring. However, it decreased endothelium-dependent relaxations induced by acetylcholine in male offspring but increased them in females. There were no differences in eNOS protein levels in aortas between the control and nicotinetreated animals in either male or female offspring. The results suggest that fetal and neonatal nicotine exposure alters vascular functions in adult offspring in a gender-specific manner, which may lead to an increased risk of cardiovascular dysfunction in later life.

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Section: Discussionsupporting

confidence: 90%

Fetal and Neonatal Nicotine Exposure Differentially Regulates Vascular Contractility in Adult Male and Female Offspring

Xiao¹,

Huang²,

Lawrence³

et al. 2006

J Pharmacol Exp Ther

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“…At P8, pups received the last treatment (2 mg/ kg) in the morning and were sacrificed 30 min later. Control animals were intubated without formula to prevent large differences in weight gain between the control and the nicotine treatment group, which result from nicotine's anorexic effect (Huang et al, 2006). The dose used in the present study (6 mg/kg/day) resulted in nicotine blood serum levels of 100 to 150 ng/ml (unpublished results), roughly equivalent to nicotine levels in heavy smokers using three packs per day (Murrin et al, 1987).…”

Section: Animal and Drug Administrationmentioning

confidence: 83%

“…Oral gastric intubation with nicotine was administered as described in Huang et al, 2006. Briefly, (-)-nicotine liquid (Sigma N3876) was dissolved in formula (Enfamil® with iron).…”

Section: Animal and Drug Administrationmentioning

confidence: 99%

“…To evaluate the effects of chronic neonatal nicotine treatment (CNN) during a developmental period which corresponds to the third trimester in humans and is characterized by rapid brain growth (Dobbing and Sands, 1979), we developed an oral gastric intubation model (Huang and et al, 2006). In this study, we compared the effects of CNN on nAChR binding sites, subunit mRNA expression, morphological properties and apoptotic markers in hippocampus and cerebellum.…”

Section: Introductionmentioning

confidence: 99%

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Effects of chronic neonatal nicotine exposure on nicotinic acetylcholine receptor binding, cell death and morphology in hippocampus and cerebellum

2007

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Nicotine, the major psychoactive ingredient in tobacco interacting with nicotinic acetylcholine receptors (nAChR), is believed to have neuroprotective and neurotoxic effects on the developing brain. Neurotoxicity has been attributed to activation of homomeric α7 nAChRs, neuroprotection to heteromeric α4β2 nAChRs. Thus, developmental nicotine could have opposite effects in different brain regions, depending on nAChR subtype expression. Here, we determined if chronic neonatal nicotine exposure (CNN), during a period of brain growth corresponding to the third human trimester, differentially regulates nAChR expression, cell death, and morphological properties in hippocampus and cerebellum, two structures maturing postnatally. Rat pups were orally treated with 6 mg/kg/day nicotine from postnatal day (P)1 to P7. On P8, expression for α4, α7 and β2 mRNA was determined by in situ hybridization; nAChR binding sites in by receptor autoradiography, dying neurons by TUNEL and Fluoro-Jade staining and morphological properties by analysis of Cresyl-Violet stained sections. In control cerebellum, strong expression of α4, β2 mRNA and heteromeric nAChRs labeled with [ 125 I]-Epibatidine were found in granule cells, and α7 mRNA and homomeric nAChRs labeled with [ 125 I]-αBungarotoxin in the external germinal layer. In control hippocampus, low expression of α4 mRNA and heteromeric nAChRs and high expression of α7 mRNA and homomeric nAChRs were detected. CNN increased heteromeric nAChR binding in hippocampus but not cerebellum and significantly decreased neuronal soma size and increased packing density in hippocampal principal cells but not in cerebellum. CNN did not increase the number of dying cells in any area, but significantly fewer TUNEL-labeled cells were found in CA3 strata oriens and radiatum and cerebellar granule layer. Thus, the hippocampus seems to be more sensitive than the cerebellum to CNN which could result from different nAChR subtype expression and might explain long-lasting altered cognitive functions correlated with gestational nicotine exposure due to changes in hippocampal cell morphology.

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“…Direct exposure-via subcutaneous (s.c. 1 ) injections (Segarra and Strand 1989), oral gavage (Gilbertson and Barron 2005;Huang et al 2006), or gastrostomy tubes (Girard et al 2001;Thomas et al 2000)-affords the opportunity to study the effects of drugs directly on offspring development, independent of maternal physiology, and to determine the consequences of nicotine on developing parameters (Girard et al 2001). However, s.c. injections are stressful, making it diffi cult to separate drug effects from the stress of injection, and nicotine-induced changes in the pups may alter maternal behavior when they are returned to the litter.…”

Section: Neonatal Exposurementioning

confidence: 99%

Effects of Pre- and Neonatal Nicotine Exposure in Rodents: Inconsistent Evidence

Sobrian¹,

Holson²

2011

ILAR Journal

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This review presents an analysis of the literature on behavioral effects of developmental exposure to nicotine, as assessed in rodent models that mimic the consequences for human offspring of maternal cigarette smoking. Despite the frequency of reports of low birth weight, hyperactivity, cognitive deficits, and psychiatric problems, inconsistencies exist in both the clinical and experimental literature. Confounding socioeconomic and other demographic variables may account for discrepancies in clinical reports, and the choice of developmental exposure period and the method of nicotine administration may explain differences in experimental outcomes. Analysis of a number of variables (e.g., physical, behavioral, and cognitive) shows that fetal exposure to nicotine does not consistently cause growth retardation or decreased birth weight, nor reliably affect motor activity. But combined pre- and neonatal exposure is likely to result in delayed reflex development, global impairments in learning and memory, and an increased incidence of symptoms that model psychiatric illness. There is also support for increased self-administration of nicotine and other drugs of abuse in animals exposed developmentally to nicotine, as well as potent effects on offspring responses to drug challenges. Unlike reports in the clinical literature, sexually dimorphic effects were not evident in most animal models. Possible neuroanatomical and cholinergic mechanisms responsible for behavioral changes are briefly discussed. Statistical and design considerations are provided to increase the translational value of this research and, most importantly, enhance the replicability of reported findings.

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Chronic nicotine induces growth retardation in neonatal rat pups

Cited by 32 publications

References 78 publications

Fetal and Neonatal Nicotine Exposure Differentially Regulates Vascular Contractility in Adult Male and Female Offspring

Fetal and Neonatal Nicotine Exposure Differentially Regulates Vascular Contractility in Adult Male and Female Offspring

Effects of chronic neonatal nicotine exposure on nicotinic acetylcholine receptor binding, cell death and morphology in hippocampus and cerebellum

Effects of Pre- and Neonatal Nicotine Exposure in Rodents: Inconsistent Evidence

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