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


: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 projections in developing rats. Terbutaline administration on postnatal days 2-5 led to immediate and persistent deficiencies in cardiac norepinephrine levels, with greater effects in males than in females. The liver showed a lesser effect; we reasoned that the tissue differences could represent participation of retrograde trophic signaling from the postsynaptic site to the developing neuronal projection, since hepatic β2-adrenoceptors decline in the perinatal period. Accordingly, when we gave terbutaline earlier, on gestational days 17-20, we saw the same deficiencies in hepatic norepinephrine that had been seen in the heart with the later administration paradigm. Administration of isoproterenol, which stimulates both β1- and β2-subtypes, also had trophic effects that differed in direction and critical period from those elicited by terbutaline; methoxamine, which stimulates α1-adrenoceptors, was without effect. Thus, terbutaline, operating through trophic interactions with β2-adrenoceptors, impairs development of noradrenergic projections in a manner similar to that previously reported for its effects on the same neurotransmitter systems in the immature cerebellum. Our results point to the likelihood of autonomic dysfunction in individuals exposed prenatally to terbutaline; in light of the connection between terbutaline and autism, these results could also contribute to autonomic dysregulation seen in children with this disorder.


Neurotoxicol Teratol


Slotkin TA,Seidler FJ




Has Abstract


2013-03-01 00:00:00












  • Effect of sulfite on cognitive function in normal and sulfite oxidase deficient rats.

    abstract::Sulfites, which are commonly used as preservatives, are continuously formed in the body during metabolism of sulfur-containing amino acids. Sulfite is oxidized to sulfate ion by sulfite oxidase (SOX, EC. The aim of this study was to investigate the possible toxic effects of sulfite on neurons by measuring ac...

    journal_title:Neurotoxicology and teratology

    pub_type: 杂志文章


    authors: Küçükatay V,Savcioğlu F,Hacioğlu G,Yargiçoğlu P,Ağar A

    更新日期:2005-01-01 00:00:00

  • Origins of behavioral teratology and distinctions between research on pharmaceutical agents and environmental/industrial chemicals.

    abstract::Most behavioral teratology studies have focused on pharmaceutical agents. Investigations of developmental toxicity are lacking for the majority of the nearly 100,000 industrial chemicals currently in use. Only some three dozen chemicals have been examined for behavioral/neurochemical deviations in offspring following ...

    journal_title:Neurotoxicology and teratology

    pub_type: 杂志文章,评审


    authors: Nelson BK

    更新日期:1990-07-01 00:00:00

  • Thermoregulatory effects of chlorpyrifos in the rat: long-term changes in cholinergic and noradrenergic sensitivity.

    abstract::Subcutaneous injection of a sublethal dose of chlorpyrifos (CHLP), an organophosphate (OP) pesticide, causes long-term inhibition in cholinesterase activity (ChE) of brain, blood, and other tissues. Such prolonged inhibition in ChE should lead to marked behavioral and autonomic thermoregulatory patterns, especially in...

    journal_title:Neurotoxicology and teratology

    pub_type: 杂志文章


    authors: Gordon CJ

    更新日期:1994-01-01 00:00:00

  • Development of neurons and synapses in ochratoxin A-induced microcephalic mice: a quantitative assessment of somatosensory cortex.

    abstract::Ochratoxin A (a mycotoxin) is known to cause cell death in the developing brain of embryos 1-2 days after treatment. Microcephaly was observed with high frequency in mice by prenatal treatment with ochratoxin A. Using a stereological method, the numerical densities of neurons and synapses were investigated in the soma...

    journal_title:Neurotoxicology and teratology

    pub_type: 杂志文章


    authors: Fukui Y,Hayasaka S,Itoh M,Takeuchi Y

    更新日期:1992-05-01 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

  • Zebrafish as potential model for developmental neurotoxicity testing: a mini review.

    abstract::The zebrafish is a powerful toxicity model; biochemical assays can be combined with observations at a structural and functional level within one individual. This mini review summarises the potency of zebrafish as a model for developmental neurotoxicity screening, and its possibilities to investigate working mechanisms...

    journal_title:Neurotoxicology and teratology

    pub_type: 杂志文章,评审


    authors: de Esch C,Slieker R,Wolterbeek A,Woutersen R,de Groot D

    更新日期:2012-11-01 00:00:00

  • Breast-feeding and gender as moderators of teratogenic effects on cognitive development.

    abstract::Researchers in the Netherlands have reported that the associations of prenatal polychlorinated biphenyl (PCB) exposure with poorer cognitive performance in childhood are generally stronger and statistically significant only among non-breast-fed children. This paper reports a similar pattern of greater vulnerability am...

    journal_title:Neurotoxicology and teratology

    pub_type: 杂志文章


    authors: Jacobson JL,Jacobson SW

    更新日期:2002-05-01 00:00:00

  • Prenatal cocaine exposure and postnatal hypoxia independently decrease carotid body dopamine in neonatal rats.

    abstract::The effects of prenatal cocaine exposure on the levels of carotid body dopamine (DA) and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were investigated in 5-day-old rat pups exposed to normoxic and hypoxic conditions. Timed-pregnant Sprague-Dawley rats were injected b.i.d. with ei...

    journal_title:Neurotoxicology and teratology

    pub_type: 杂志文章


    authors: Lipton JW,Yuengsrigul A,Ling ZD,Weese-Mayer DE,Carvey PM

    更新日期:1996-05-01 00:00:00

  • Reduced neuronal proliferation by proconvulsant drugs in the developing zebrafish brain.

    abstract::Seizures have been reported to modify neural development in the immature brain. In this study, we attempted to determine whether pentylenetetrazol (a GABAergic receptor antagonist, PTZ)-induced seizures influence cell proliferation in zebrafish larvae (5 and 15 days of post-fertilization), using bromodeoxyuridine (Brd...

    journal_title:Neurotoxicology and teratology

    pub_type: 杂志文章


    authors: Kim YH,Lee Y,Lee K,Lee T,Kim YJ,Lee CJ

    更新日期:2010-09-01 00:00:00

  • Decreased sensitivity in adolescent vs. adult rats to the locomotor activating effects of toluene.

    abstract::Volatile organic solvent (inhalant) abuse continues to be a major health concern throughout the world. Of particular concern is the abuse of inhalants by adolescents because of its toxicity and link to illicit drug use. Toluene, which is found in many products such as glues and household cleaners, is among the most co...

    journal_title:Neurotoxicology and teratology

    pub_type: 杂志文章


    authors: Bowen SE,Charlesworth JD,Tokarz ME,Wright MJ Jr,Wiley JL

    更新日期:2007-11-01 00:00:00

  • Motor assessment of cocaine/polydrug exposed infants at age 4 months.

    abstract::Fifty nondrug-exposed infants and 74 cocaine/polydrug-exposed infants were evaluated on the Movement Assessment of Infants (MAI). The test provides an assessment of risk for motor dysfunction at age 4 months. There was a significant difference in total risk scores between the two groups of infants with cocaine-exposed...

    journal_title:Neurotoxicology and teratology

    pub_type: 杂志文章


    authors: Schneider JW,Chasnoff IJ

    更新日期:1992-03-01 00:00:00

  • Pyrethroid effects on schedule-controlled behavior: time and dosage relationships.

    abstract::Pyrethroid insecticides have been divided into Types I and II based on behavioral profiles of toxicity produced by life-threatening dosages. In order to assess potential alterations in acquired (operant) behavior, acute dosage-effect and time-course determinations for permethrin (Type I) and cypermethrin (Type II) wer...

    journal_title:Neurotoxicology and teratology

    pub_type: 杂志文章


    authors: Peele DB,Crofton KM

    更新日期:1987-09-01 00:00:00

  • Dysmorphic and anthropometric outcomes in 6-year-old prenatally cocaine-exposed children.

    abstract::Dysmorphologic and anthropometric assessments were performed on 154 6-year-old children prenatally exposed to cocaine (PCE) and 131 high-risk controls (NCE) of similar race and social class. Adjusted mean height z scores demonstrated a dose-response with metahydroxybenzoylecgonine above a threshold of 100 ng/g of meco...

    journal_title:Neurotoxicology and teratology

    pub_type: 杂志文章


    authors: Minnes S,Robin NH,Alt AA,Kirchner HL,Satayathum S,Salbert BA,Ellison L,Singer LT

    更新日期:2006-01-01 00:00:00

  • Developmental exposure to an organophosphate flame retardant alters later behavioral responses to dopamine antagonism in zebrafish larvae.

    abstract::Human exposure to organophosphate flame retardants (OPFRs) is widespread, including pregnant women and young children with whom developmental neurotoxic risk is a concern. Given similarities of OPFRs to organophosphate (OP) pesticides, research into the possible neurotoxic impacts of developmental OPFR exposure has be...

    journal_title:Neurotoxicology and teratology

    pub_type: 杂志文章


    authors: Oliveri AN,Ortiz E,Levin ED

    更新日期:2018-01-01 00:00:00

  • Moderate alcohol consumption during pregnancy and the incidence of fetal malformations: a meta-analysis.

    abstract::To determine whether there is an association between moderate alcohol consumption in the first trimester of pregnancy and increased risk of fetal malformations, we conducted a literature search using Medline (1966-present), PsycLit (1974-1995), and EMBASE (1988-1995). The following inclusion criteria were used to sele...

    journal_title:Neurotoxicology and teratology

    pub_type: 杂志文章,meta分析


    authors: Polygenis D,Wharton S,Malmberg C,Sherman N,Kennedy D,Koren G,Einarson TR

    更新日期:1998-01-01 00:00:00

  • Experience during adolescence shapes brain development: From synapses and networks to normal and pathological behavior.

    abstract::Adolescence is a period of dramatic neural reorganization creating a period of vulnerability and the possibility for the development of psychopathology. The maturation of various neural circuits during adolescence depends, to a large degree, on one's experiences both physical and psychosocial. This occurs through a pr...

    journal_title:Neurotoxicology and teratology

    pub_type: 杂志文章,评审


    authors: Dow-Edwards D,MacMaster FP,Peterson BS,Niesink R,Andersen S,Braams BR

    更新日期:2019-01-01 00:00:00

  • Long-term effects of acute perinatal asphyxia on rat maternal behavior.

    abstract::In this study we used a rat model of graded perinatal asphyxia to study the long-term consequences of this manipulation on rat maternal behavior at adulthood. Rats were delivered by cesarean (C) section and the pups, still in the uterus horns, were placed into a water bath at 37 degrees C for periods of 0 (controls) o...

    journal_title:Neurotoxicology and teratology

    pub_type: 杂志文章


    authors: Cirulli F,Bonsignore LT,Venerosi A,Valanzano A,Chiarotti F,Alleva E

    更新日期:2003-09-01 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

  • 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

  • Effects of bromantan on offspring maturation and development of reflexes.

    abstract::Bromantan (N-[2-adamantil]-N-[para-bromphenyl]amine) is an "actoprotective" drug widely used in Russia as a muscle performance-enhancing agent for sportsmen and as an immunostimulator in medicine. Experiments were conducted to determine whether this compound has adverse effects on the reproduction and development of o...

    journal_title:Neurotoxicology and teratology

    pub_type: 杂志文章


    authors: Iezhitsa IN,Spasov AA,Bugaeva LI

    更新日期:2001-03-01 00:00:00

  • GABAA overactivation potentiates the effects of NMDA blockade during the brain growth spurt in eliciting locomotor hyperactivity in juvenile mice.

    abstract::Both NMDA receptor blockade and GABAA receptor overactivation during the brain growth spurt may contribute to the hyperactivity phenotype reminiscent of attention-deficit/hyperactivity disorder. Here, we evaluated the effects of exposure to MK801 (a NMDA antagonist) and/or to muscimol (a GABAA agonist) during the brai...

    journal_title:Neurotoxicology and teratology

    pub_type: 杂志文章


    authors: Oliveira-Pinto J,Paes-Branco D,Cristina-Rodrigues F,Krahe TE,Manhães AC,Abreu-Villaça Y,Filgueiras CC

    更新日期:2015-07-01 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

  • A new look at quantifying tobacco exposure during pregnancy using fuzzy clustering.

    abstract:BACKGROUND:Prenatal tobacco exposure is a risk factor for the development of externalizing behaviors and is associated with several adverse health outcomes. Because pregnancy smoking is a complex behavior with both daily fluctuations and changes over the course of pregnancy, quantifying tobacco exposure is a significan...

    journal_title:Neurotoxicology and teratology

    pub_type: 杂志文章


    authors: Fang H,Johnson C,Stopp C,Espy KA

    更新日期:2011-01-01 00:00:00

  • Neurobehavioral deficits in neonatal rhesus monkeys exposed to cocaine in utero.

    abstract::In spite of significant efforts, the neurobehavioral deficits in infants born from cocaine-abusing mothers have not been clearly defined. In the present study, we examined the presence of these abnormalities in a rhesus monkey model of prenatal cocaine exposure using a nonhuman primate adaptation of the Neonatal Behav...

    journal_title:Neurotoxicology and teratology

    pub_type: 杂志文章


    authors: He N,Bai J,Champoux M,Suomi SJ,Lidow MS

    更新日期:2004-01-01 00:00:00

  • Optic nerve hypoplasia in an acute exposure model of the fetal alcohol syndrome.

    abstract::The effects of acute prenatal exposure to ethanol on the postnatal optic nerve have been examined in a C57B1/6J mouse model. Pregnant mice were exposed by intraperitoneal injection to ethanol (25% ethanol, each dose at 0.015 ml/g separated by 4 h), or to saline on the 8th gestational day and the optic nerve examined a...

    journal_title:Neurotoxicology and teratology

    pub_type: 杂志文章


    authors: Ashwell KW,Zhang LL

    更新日期:1994-03-01 00:00:00

  • N-methylation underlying Parkinson's disease.

    abstract::The discovery of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) leads to the hypothesis that Parkinson's disease (PD) is maybe initiated or precipitated by environmental or endogenous toxins by the mechanism similar to that of MPTP in genetically-predisposed individuals. Endogenous analogs of MPTP, such as beta-c...

    journal_title:Neurotoxicology and teratology

    pub_type: 杂志文章,评审


    authors: Matsubara K,Aoyama K,Suno M,Awaya T

    更新日期:2002-09-01 00:00:00

  • Effects of lifelong dietary exposure to genistein or nonylphenol on amphetamine-stimulated striatal dopamine release in male and female rats.

    abstract::Estrogen modulates baseline and amphetamine-stimulated dopamine (DA) release in the adult female rat striatum. The isoflavone found in soybeans, genistein, is a phytoestrogen and may have comparable effects on striatal DA levels. Similarly, the industrial intermediate and potential endocrine disrupter, para-nonylpheno...

    journal_title:Neurotoxicology and teratology

    pub_type: 杂志文章


    authors: Ferguson SA,Flynn KM,Delclos KB,Newbold RR,Gough BJ

    更新日期:2002-01-01 00:00:00

  • Effects of monensin feeding during development on female rats and their offspring.

    abstract::Monensin, a growth-promoting agent and coccidiostat used in veterinary medicine, was studied in terms of its effects on the development of female rats and their offspring when added to the diet. Young female rats received 100 or 300 ppm monensin mixed with powdered chow diet until adulthood, when they were mated and t...

    journal_title:Neurotoxicology and teratology

    pub_type: 杂志文章


    authors: de Souza Spinosa H,Nicolau A,Maruo VM,Bernardi MM

    更新日期:1999-07-01 00:00:00

  • Transplacental cocaine exposure. 2: Effects of cocaine dose and gestational timing.

    abstract::We have utilized a mouse model of transplacental cocaine exposure to investigate the effects of cocaine dose and gestational timing in altering brain and body growth and postnatal behavior in exposed offspring. Pregnant dams were injected with cocaine HCl at 40 mg/kg/day (COC 40) or 20 mg/kg/day (COC 20), or 10 mg/kg/...

    journal_title:Neurotoxicology and teratology

    pub_type: 杂志文章


    authors: Wilkins AS,Jones K,Kosofsky BE

    更新日期:1998-05-01 00:00:00

  • A fostering/crossfostering analysis of the effects of prenatal ethanol exposure in a liquid diet on offspring development and behavior in rats.

    abstract::Pregnant Long-Evans rats were fed a liquid diet containing either 35% ethanol-derived calories (group E) or were pair-fed to group E dams using the same diet with an equivalent amount of sucrose-derived calories (group PFC) on days 7-18 of gestation. At birth half the litters were fostered to other dams of the same tr...

    journal_title:Neurotoxicology and teratology

    pub_type: 杂志文章


    authors: Vorhees CV

    更新日期:1989-03-01 00:00:00