Prenatal nicotine exposure in rhesus monkeys compromises development of brainstem and cardiac monoamine pathways involved in perinatal adaptation and sudden infant death syndrome: amelioration by vitamin C.


:Maternal smoking during pregnancy greatly enhances perinatal morbidity/mortality and is the major risk factor for Sudden Infant Death Syndrome (SIDS). Studies in developing rodents indicate that nicotine is a neuroteratogen that targets monoamine pathways involved in the responses to hypoxia that are in turn, hypothesized to contribute to these adverse events. 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; we examined neurochemical parameters immediately after Cesarean delivery at the end of the exposure period. Nicotine evoked elevations in brainstem serotonin levels and serotonin turnover, indicating hyperactivity of these pathways. The same treatment evoked a deficit in cardiac norepinephrine levels. Both effects were offset by coadministration of the antioxidant, Vitamin C. Brainstem serotonin hyperinnervation is a hallmark of SIDS, and the hyperactivity seen here can also account for the downregulation of serotonin receptors noted in this disorder. Deficient cardiac sympathetic innervation is also consistent with increased vulnerability to hypoxia during delivery or in the agonal event in SIDS. Our results thus indicate that nicotine exposure in a primate model produces brainstem and autonomic abnormalities of the key monoamine systems that govern the response to hypoxia, indicate an important role of oxidative stress in the adverse effects, and point to potential amelioration strategies that could offset these particular effects of nicotine.


Neurotoxicol Teratol


Slotkin TA,Seidler FJ,Spindel ER




Has Abstract


2011-05-01 00:00:00














  • Aluminum produces age related behavioral toxicity in the rabbit.

    abstract::Two- to 3.4-year-old, retired breeder, rabbits received repeated aluminum (Al) lactate or sodium (Na) lactate injections. All six rabbits receiving twenty 400 mumol Al/kg SC injections died, demonstrating much higher mortality than previously seen in younger rabbits. Subsequent rabbits receiving Al were dosed with 200...

    journal_title:Neurotoxicology and teratology

    pub_type: 杂志文章


    authors: Yokel RA

    更新日期:1989-05-01 00:00:00

  • Effects of exposure to PCBs and related compounds on growth and activity in children.

    abstract::Two hundred thirty-six children from two established cohorts at risk for exposure to polychlorinated biphenyls (PCBs) and related contaminants were evaluated at age 4 years. Prenatal exposure (assessed by cord serum PCB level) was associated with lower weight, an effect consistent with reports of growth retardation in...

    journal_title:Neurotoxicology and teratology

    pub_type: 杂志文章


    authors: Jacobson JL,Jacobson SW,Humphrey HE

    更新日期:1990-07-01 00:00:00

  • Schedule-controlled operant behavior of rats during 1,1,1-trichloroethane inhalation: relationship to blood and brain solvent concentrations.

    abstract::The central nervous system is the principal target of 1,1,1-trichloroethane (TRI), and several studies of this volatile solvent have demonstrated effects on learned animal behaviors. There have been few attempts, however, to quantitatively relate such effects to blood or target organ (brain) solvent concentrations. Th...

    journal_title:Neurotoxicology and teratology

    pub_type: 杂志文章


    authors: Warren DA,Reigle TG,Muralidhara S,Dallas CE

    更新日期:1998-03-01 00:00:00

  • Euthanasia by decapitation: evidence that this technique produces prompt, painless unconsciousness in laboratory rodents.

    abstract::Rapid euthanasia of laboratory rodents without the use of anesthesia is a necessary research technique whenever there is the likelihood of anesthesia or stress interfering with the chemistry of the tissues under investigation. Decapitation has long been the procedure of choice under such circumstances. Recently, howev...

    journal_title:Neurotoxicology and teratology

    pub_type: 指南,杂志文章


    authors: Holson RR

    更新日期:1992-07-01 00:00:00

  • Characterization of performance on an automated visual recognition memory task in 7.5-month-old infants.

    abstract::Infant looking behaviors measured during visual assessment paradigms may be more reliable predictors of long-term cognitive outcomes than standard measures such as the Bayley Scales of Infant Development typically used in environmental epidemiology. Infrared eye tracking technology offers an innovative approach to aut...

    journal_title:Neurotoxicology and teratology

    pub_type: 杂志文章


    authors: Dzwilewski KLC,Merced-Nieves FM,Aguiar A,Korrick SA,Schantz SL

    更新日期:2020-01-01 00:00:00

  • Effects of prenatal cocaine on behavioral adaptation to chronic stress in adult rats.

    abstract::Prenatal exposure to cocaine in rats has previously been shown to alter the behavioral and hormonal responses to acute stressors, although no work has yet examined stress adaptation in these animals in adulthood, a possibility examined in this experiment. Male and female offspring of Sprague-Dawley rat dams given 40 m...

    journal_title:Neurotoxicology and teratology

    pub_type: 杂志文章


    authors: Campbell JO,Bliven TD,Silveri MM,Snyder KJ,Spear LP

    更新日期:2000-11-01 00:00:00

  • Effects of repeated administration of soman on schedule-controlled behavior and brain in the rat.

    abstract::The effects of repeated SC administration of soman on schedule-controlled performance and brain pathology were studied in the rat. Soman suppressed response rates in both components of a multiple fixed interval 50-sec fixed-ratio 25 (mult. FI 50-sec FR 25) schedule of reinforcement, although all animals revealed marke...

    journal_title:Neurotoxicology and teratology

    pub_type: 杂志文章


    authors: Hymowitz N,Ploshnick A,Laemle L,Brezenoff H

    更新日期:1990-01-01 00:00:00

  • Low-level Pb and cardiovascular responses to acute stress in children: the role of cardiac autonomic regulation.

    abstract:OBJECTIVE:A number of studies suggest that Pb exposure increases cardiovascular disease risk in humans. As a potential mechanism for this effect, we recently reported a significant association between early childhood Pb levels and cardiovascular response to acute stress. The current study considers the association betw...

    journal_title:Neurotoxicology and teratology

    pub_type: 杂志文章


    authors: Gump BB,Mackenzie JA,Bendinskas K,Morgan R,Dumas AK,Palmer CD,Parsons PJ

    更新日期:2011-03-01 00:00:00

  • Toluene-induced hearing loss in acivicin-treated rats.

    abstract::Toluene can be considered an ototoxic chemical compound in the rat. Outer hair cells are particularly sensitive to this aromatic organic solvent or to one of its metabolites. The objective of the present study was to evaluate the possible role played by cysteine S-conjugates in the ototoxic process in Long-Evans rats....

    journal_title:Neurotoxicology and teratology

    pub_type: 杂志文章


    authors: Waniusiow D,Campo P,Cossec B,Cosnier F,Grossman S,Ferrari L

    更新日期:2008-05-01 00:00:00

  • 3-Nitropropionic acid produces indirect excitotoxic damage to rat striatum.

    abstract::The mechanism of striatal damage induced by 3-nitropropionic acid (3-NPA) was studied in rats by neuropathological and neurochemical methods. Neuronal shrinkage with astrogliosis was observed in striatum after local injection of 0.5-5 mumol 3-NPA. Decortications involving dorsal and lateral aspects of frontal cortex o...

    journal_title:Neurotoxicology and teratology

    pub_type: 杂志文章


    authors: Fu Y,He F,Zhang S,Huang J,Zhang J,Jiao X

    更新日期:1995-05-01 00:00:00

  • Prenatal cocaine use and maternal depression: effects on infant neurobehavior.

    abstract:OBJECTIVE:The present study examined the impact of both perinatal maternal depression and cocaine use on infant neurobehavior at 1 month of age in a large, multi-site study. METHODS:Infant neurobehavior was examined in 1053 infants at 1 month of age using the NICU Network Neurobehavioral Scale (NNNS). Mothers were int...

    journal_title:Neurotoxicology and teratology

    pub_type: 杂志文章,多中心研究


    authors: Salisbury AL,Lester BM,Seifer R,Lagasse L,Bauer CR,Shankaran S,Bada H,Wright L,Liu J,Poole K

    更新日期:2007-05-01 00:00:00

  • Formamidine pesticides enhance susceptibility to kindled seizures in amygdala and hippocampus of the rat.

    abstract::Electrical kindling of the amygdala and hippocampus was used to evaluate the effects of two formamidines, chlordimeform (CDF) and amitraz (AMZ), upon seizures susceptibility in the rat. Male Long-Evans rats were implanted with electrodes in the amygdala or dorsal dentate gyrus, and injected IP daily with 40 mg/kg CDF,...

    journal_title:Neurotoxicology and teratology

    pub_type: 杂志文章


    authors: Gilbert ME

    更新日期:1988-05-01 00:00:00

  • Impaired glutamatergic and GABAergic transmission by amitraz in primary hippocampal cells.

    abstract::Amitraz is a formamidine pesticide that has been reported to be a neurotoxic compound that induces convulsions among other effects. Excitatory and inhibitory neurotransmission is mediated mainly by glutamate and GABA, respectively, so their alteration could be responsible for induction of seizures. In this regard, ami...

    journal_title:Neurotoxicology and teratology

    pub_type: 杂志文章


    authors: Del Pino J,Frejo MT,Baselga MJ,Moyano P,Díaz MJ

    更新日期:2015-07-01 00:00:00

  • Ethanol-induced cell death in cultured rat astroglia.

    abstract::Because of the important role of glial cells in brain maturation and reports on their delayed proliferation following ethanol exposure, it was considered of interest to investigate the mechanism of ethanol action on these cells. Biochemical parameters related to the apoptotic and necrotic processes in astroglial cells...

    journal_title:Neurotoxicology and teratology

    pub_type: 杂志文章


    authors: Holownia A,Ledig M,Ménez JF

    更新日期:1997-03-01 00:00:00

  • Methamphetamine-induced dopamine and serotonin reductions in neostriatum are not gender specific in rats with comparable hyperthermic responses.

    abstract::Methamphetamine (MA)-induced monoamine depletions in male and female Sprague-Dawley CD rats were studied under conditions in which the magnitude of MA-induced hyperthermia was comparable between the sexes. MA (5 or 10 mg/kg) or saline (3 ml/kg) was administered SC four times at 2-h intervals. Animals were sacrificed 3...

    journal_title:Neurotoxicology and teratology

    pub_type: 杂志文章


    authors: Fukumura M,Cappon GD,Broening HW,Vorhees CV

    更新日期:1998-07-01 00:00:00

  • Differential effects on cognitive functioning in 13- to 16-year-olds prenatally exposed to cigarettes and marihuana.

    abstract::Cognitive performance was examined in 145 thirteen- to sixteen-year-old adolescents for whom prenatal exposure to marihuana and cigarettes had been ascertained. The subjects were from a low-risk, predominantly middle-class sample participating in an ongoing, longitudinal study. The assessment battery included tests of...

    journal_title:Neurotoxicology and teratology

    pub_type: 杂志文章


    authors: Fried PA,Watkinson B,Gray R

    更新日期:2003-07-01 00:00:00

  • Ototoxicity of the three xylene isomers in the rat.

    abstract::Numerous experiments have shown that the aromatic solvents can affect the auditory system in the rat, the cochlea being targeted first. Solvents differ in cochleotoxic potency: for example, styrene is more ototoxic than toluene or xylenes. The goal of this study was to determine the relative ototoxicity of the three i...

    journal_title:Neurotoxicology and teratology

    pub_type: 杂志文章


    authors: Maguin K,Lataye R,Campo P,Cossec B,Burgart M,Waniusiow D

    更新日期:2006-11-01 00:00:00

  • Terbutaline impairs the development of peripheral noradrenergic projections: potential implications for autism spectrum disorders and pharmacotherapy of preterm labor.

    abstract::Terbutaline, a β2-adrenoceptor agonist, is used off-label for long-term management of preterm labor; such use is associated with increased risk of neurodevelopmental disorders, including autism spectrum disorders. We explored the mechanisms underlying terbutaline's effects on development of peripheral sympathetic proj...

    journal_title:Neurotoxicology and teratology

    pub_type: 杂志文章


    authors: Slotkin TA,Seidler FJ

    更新日期:2013-03-01 00:00:00

  • Somatic mitochondrial DNA mutations do not increase neuronal vulnerability to MPTP in young POLG mutator mice.

    abstract::Mitochondrial DNA (mtDNA) mutations are hypothesized to play a pathogenic role in aging and age-related neurodegenerative diseases such as Parkinson's disease (PD). In support of this, high levels of somatic mtDNA mutations in “POLG mutator” mice carrying a proofreading-deficient form of mtDNA polymerase ã (Polg(D257A...

    journal_title:Neurotoxicology and teratology

    pub_type: 杂志文章


    authors: Dai Y,Clark J,Zheng K,Kujoth GC,Prolla TA,Simon DK

    更新日期:2014-11-01 00:00:00

  • Repeated measures designs in behavioral toxicology: application to chronic marijuana smoke exposure.

    abstract::This paper discusses the application of repeated measures methods in the statistical analysis of an experiment in behavioral toxicology. The chronic marijuana smoke exposure study conducted at the National Center for Toxicological Research is used for an example of the types of problems that one encounters in analyzin...

    journal_title:Neurotoxicology and teratology

    pub_type: 杂志文章


    authors: Allen RR,Slikker W Jr,Paule MG

    更新日期:1990-09-01 00:00:00

  • Does chronic prenatal methadone exposure affect beta-receptor subtypes in placental, fetal and maternal brain homogenates?

    abstract::Computer competition analysis of 3H-DHA (3H-dihydroalprenolol, a nonselective beta-adrenergic radioligand) binding in the presence of unlabeled metoprolol (a beta 1-selective antagonist) indicates the existence of both beta 1- and beta 2-adrenergic receptor subtypes in the rat placenta and confirms previous reports th...

    journal_title:Neurotoxicology and teratology

    pub_type: 杂志文章


    authors: Darmani NA,Schnoll SH,Fuchs B,Martin BR

    更新日期:1991-01-01 00:00:00

  • Developmental neurotoxicity evaluation of the avermectin pesticide, emamectin benzoate, in Sprague-Dawley rats.

    abstract::The potential of emamectin benzoate (EB) to cause developmental neurotoxicity in Sprague-Dawley rats was assessed using a study design by the US EPA. Dosages of 0 (deionized water), 0.1, 0.6, or 3.6 mg/kg/day were administered at 5 ml/kg by oral gavage from gestational day (GD) 6 to lactational day (LD) 20 to groups o...

    journal_title:Neurotoxicology and teratology

    pub_type: 杂志文章


    authors: Wise LD,Allen HL,Hoe CM,Verbeke DR,Gerson RJ

    更新日期:1997-07-01 00:00:00

  • Developmental toxicity of the environmental pollutant 4-nonylphenol in zebrafish.

    abstract::4-Nonylphenol (4-NP), an estrogen mimicking compound is produced by biodegradation of alkylethoxylates. It is well established that 4-NP can affect the development of aquatic animals by disrupting the endocrine signals. Here we show for the first time in zebrafish that 4-NP does not only target the neuroendocrine syst...

    journal_title:Neurotoxicology and teratology

    pub_type: 杂志文章


    authors: Chandrasekar G,Arner A,Kitambi SS,Dahlman-Wright K,Lendahl MA

    更新日期:2011-11-01 00:00:00

  • Infants of drug addicts: at risk for child abuse, neglect, and placement in foster care.

    abstract::In a methadone maintenance program for pregnant, drug dependent women, an investigation was undertaken (1) to study the occurrence of violence experienced by the women as children and as adults and (2) to lean whether those who report past violence/abuse are more likely to neglect and/or abandon their children to the ...

    journal_title:Neurotoxicology and teratology

    pub_type: 杂志文章


    authors: Regan DO,Ehrlich SM,Finnegan LP

    更新日期:1987-07-01 00:00:00

  • Effects of high doses of toluene on color vision.

    abstract::High exposure to toluene may cause optic neuropathy and retinopathy, both associated with dyschromatopsia. Another solvent, ethanol, is known to induce acute blue-yellow dyschromatopsia. This study investigated the acute effects of high doses of toluene on color vision. Eight male printshop workers were examined befor...

    journal_title:Neurotoxicology and teratology

    pub_type: 临床试验,杂志文章


    authors: Muttray A,Wolters V,Jung D,Konietzko J

    更新日期:1999-01-01 00:00:00

  • Recommendations for harmonization of data collection and analysis of developmental neurotoxicity endpoints in regulatory guideline studies: Proceedings of workshops presented at Society of Toxicology and joint Teratology Society and Neurobehavioral Terato

    abstract::The potential for developmental neurotoxicity (DNT) of environmental chemicals may be evaluated using specific test guidelines from the US Environmental Protection Agency or the Organisation for Economic Cooperation and Development (OECD). These guidelines generate neurobehavioral, neuropathological, and morphometric ...

    journal_title:Neurotoxicology and teratology

    pub_type: 杂志文章


    authors: Li AA,Sheets LP,Raffaele K,Moser V,Hofstra A,Hoberman A,Makris SL,Garman R,Bolon B,Kaufmann W,Auer R,Lau E,Vidmar T,Bowers WJ

    更新日期:2017-09-01 00:00:00

  • Effects of acute treatment with dopaminergic drugs on open field behavior of adult monkeys treated with lead during the first year postpartum.

    abstract::A pharmacological challenge of nonhuman primate open field behavior, similar to that which previously assessed the cholinergic system (10), was used here to measure potential lead-induced alterations in the dopaminergic system. Monkeys that had been treated with lead during the first year postpartum were assessed at 7...

    journal_title:Neurotoxicology and teratology

    pub_type: 杂志文章


    authors: Ferguson SA,Felipa HN,Bowman RE

    更新日期:1996-03-01 00:00:00

  • Influence of 5-azacytidine on differentiation and growth in rat nervous system tumor cell lines.

    abstract::In vitro studies with permanent cell lines derived from ENU-induced rat CNS and PNS tumors have shown that substances acting on second messenger systems as well as glucocorticoids have a cytostatic effect at high cell densities, but enhance proliferation at low densities. The nontoxic cytostatic effects are partially ...

    journal_title:Neurotoxicology and teratology

    pub_type: 杂志文章


    authors: Stark M,Bilzer T,Inoue N,Wechsler W

    更新日期:1989-11-01 00:00:00

  • Developmental neurotoxic effects of chlorpyrifos on acetylcholine and serotonin pathways in an avian model.

    abstract::The developmental neurotoxicity of organophosphates such as chlorpyrifos (CPF) involves multiple mechanisms that ultimately compromise the function of specific neurotransmitter systems, notably acetylcholine (ACh) and serotonin (5-hydroxytryptamine, 5HT). Studies in mammalian models incorporate both direct effects on ...

    journal_title:Neurotoxicology and teratology

    pub_type: 杂志文章


    authors: Slotkin TA,Seidler FJ,Ryde IT,Yanai J

    更新日期:2008-09-01 00:00:00

  • Gene expression changes in developing zebrafish as potential markers for rapid developmental neurotoxicity screening.

    abstract::Hazard information essential to guide developmental neurotoxicity risk assessments is limited for many chemicals. As developmental neurotoxicity testing using rodents is laborious and expensive, alternative species such as zebrafish are being adapted for rapid toxicity screening. Assessing the developmental neurotoxic...

    journal_title:Neurotoxicology and teratology

    pub_type: 杂志文章


    authors: Fan CY,Cowden J,Simmons SO,Padilla S,Ramabhadran R

    更新日期:2010-01-01 00:00:00