Adrenal-mediated rather than direct effects of nicotine as a basis of altered sex steroid synthesis in fetal and neonatal rat

Sarasin, Alexander; Schlumpf, Margret; Müller, Malvina; Fleischmann, Iréne; Lauber, Markus; Lichtensteiger, W.

doi:10.1016/s0890-6238(02)00119-3

Cited by 49 publications

(34 citation statements)

References 45 publications

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“…These results are consistent with previous work with prenatal nicotine treatment, which showed male-female differences in neurochemical and behavioral outcomes and in the synthesis of sex steroids (Lichtensteiger and Schlumpf, 1985;Pauly et al, 2004;Sarasin et al, 2003;Segarra and Strand, 1989;Tizabi et al, 1997). These have distinct parallels in the effects of maternal smoking during pregnancy on behavior, which is similarly gender-selective (Fergusson et al, 1998;Wakschlag and Hans, 2002;Wakschlag et al, 1997).…”

Section: Effects Of Prenatal Nicotine Exposure On the Response To Nicsupporting

confidence: 91%

Prenatal Nicotine Exposure Alters the Responses to Subsequent Nicotine Administration and Withdrawal in Adolescence: Serotonin Receptors and Cell Signaling

Slotkin

Tate

Cousins

et al. 2005

Neuropsychopharmacol

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Offspring of women who smoke during pregnancy are themselves more likely to take up smoking in adolescence, effects that are associated with a high rate of depression and increased sensitivity to withdrawal symptoms. To evaluate the biological basis for this relationship, we assessed effects on serotonin (5-hydroxytryptamine, 5HT) receptors and 5HT-mediated cellular responses in rats exposed to nicotine throughout prenatal development and then given nicotine in adolescence (postnatal days PN30-47.5), using regimens that reproduce plasma nicotine levels found in smokers. Evaluations were then made during the period of adolescent nicotine treatment and for up to one month after the end of treatment. Prenatal nicotine exposure, which elicits damage to 5HT projections in the cerebral cortex and striatum, produced sex-selective changes in the expression of 5HT 1A and 5HT 2 receptors, along with induction of adenylyl cyclase (AC), leading to sensitization of heterologous inputs operating through this signaling pathway. Superimposed on these effects, the AC response to 5HT was shifted toward inhibition. By itself, adolescent nicotine administration, which damages the same pathways, produced similar effects on receptors and the 5HT-mediated response, but a smaller overall induction of AC. Animals exposed to prenatal nicotine showed a reduced response to nicotine administered in adolescence, results in keeping with earlier findings of persistent desensitization. Our results indicate that prenatal nicotine exposure alters parameters of 5HT synaptic communication lasting into adolescence and changes the response to nicotine administration and withdrawal in adolescence, actions which may contribute to a subpopulation especially vulnerable to nicotine dependence.

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Section: Effects Of Prenatal Nicotine Exposure On the Response To Nicsupporting

confidence: 91%

Prenatal Nicotine Exposure Alters the Responses to Subsequent Nicotine Administration and Withdrawal in Adolescence: Serotonin Receptors and Cell Signaling

Slotkin

Tate

Cousins

et al. 2005

Neuropsychopharmacol

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“…NRT, especially by transdermal patch, delivers more nicotine to the fetus than smoking does. Nicotine concentrations in fetal rat brain are 2.5 times higher than the mother's blood nicotine level when on continuous nicotine feed; a similar ratio can be expected in pregnant women using the patch (Sarasin et al, 2003). Smokers who use NRT may have nicotine concentrations up to three times higher than the approved dose (Chan, Jeremy, Stansby, & Shukla, 2004).…”

Section: The New Rulesmentioning

confidence: 90%

Critical Review

Ginzel¹,

Maritz

Marks

et al. 2007

J Health Psychol

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The recent expansion of Nicotine Replacement Therapy to pregnant women and children ignores the fact that nicotine impairs, disrupts, duplicates and/or interacts with essential physiological functions and is involved in tobacco-related carcinogenesis. The main concerns in the present context are its fetotoxicity and neuroteratogenicity that can cause cognitive, affective and behavioral disorders in children born to mothers exposed to nicotine during pregnancy, and the detrimental effects of nicotine on the growing organism. Hence, the use of nicotine, whose efficacy in treating nicotine addiction is controversial even in adults, must be strictly avoided in pregnancy, breastfeeding, childhood and adolescence.

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“…Similarly, the infusion model used here is an appropriate simulation of continuous nicotine delivery as is typical of transdermal nicotine patches, and although smokers tend to maintain a steady-state nicotine plasma level, these are likely to decay somewhat overnight when smoking ceases. A recent study showed that continuous nicotine delivery in rodents results in more than a two-fold higher fetal nicotine brain level as compared to maternal blood (Sarasin et al, 2003). Accordingly, future studies should address the impact of different modes of nicotine delivery, with and without dietary supplements, on the actual levels of nicotine achieved in fetal brain.…”

Section: Discussionmentioning

confidence: 99%

Effects of Prenatal Nicotine Exposure on Primate Brain Development and Attempted Amelioration with Supplemental Choline or Vitamin C: Neurotransmitter Receptors, Cell Signaling and Cell Development Biomarkers in Fetal Brain Regions of Rhesus Monkeys

Slotkin

Seidler

Qiao

et al. 2004

Neuropsychopharmacol

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Studies in developing rodents indicate that nicotine is a neuroteratogen that disrupts brain development by stimulating nicotinic acetylcholine receptors (nAChRs) that control neural cell replication and differentiation. We administered nicotine to pregnant Rhesus monkeys from gestational day 30 through 160 by continuous infusion, achieving maternal plasma levels comparable to those in smokers (30 ng/ml). Fetal brain regions and peripheral tissues were examined for nAChR subtypes, other neurotransmitter receptors, and indices of cell signaling and cell damage. Nicotine evoked nAChR upregulation, but with distinct regional disparities indicative of selective stimulatory responses. Similarly, indices of cell loss (reduced DNA), cell size and neuritic outgrowth (protein/DNA and membrane/total protein ratios) were distinct for each region and did not necessarily follow the rank order of nAChR upregulation, suggesting the involvement of additional mechanisms such as oxidative stress. We then attempted to offset the adverse effects of nicotine with standard dietary supplements known to interact with nicotine. By itself, choline elicited nicotine-like actions commensurate with its promotion of cholinergic neurotransmission. When given in combination with nicotine, choline protected some regions from damage but worsened nicotine's effects in other regions. Similarly, Vitamin C supplementation had mixed effects, increasing nAChR responses while providing protection from cell damage in the caudate, the brain region most susceptible to oxidative stress. Our results indicate that nicotine elicits neurodevelopmental damage that is highly selective for different brain regions, and that dietary supplements ordinarily thought to be neuroprotectant may actually worsen some of the adverse effects of nicotine on the fetal brain.

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Adrenal-mediated rather than direct effects of nicotine as a basis of altered sex steroid synthesis in fetal and neonatal rat

Cited by 49 publications

References 45 publications

Prenatal Nicotine Exposure Alters the Responses to Subsequent Nicotine Administration and Withdrawal in Adolescence: Serotonin Receptors and Cell Signaling

Prenatal Nicotine Exposure Alters the Responses to Subsequent Nicotine Administration and Withdrawal in Adolescence: Serotonin Receptors and Cell Signaling

Critical Review

Effects of Prenatal Nicotine Exposure on Primate Brain Development and Attempted Amelioration with Supplemental Choline or Vitamin C: Neurotransmitter Receptors, Cell Signaling and Cell Development Biomarkers in Fetal Brain Regions of Rhesus Monkeys

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