Prenatal Nicotine Exposure Modifies Behavior of Mice Through Early Development

Ajarem, Jamaan S.

doi:10.1016/s0091-3057(97)00408-5

Cited by 113 publications

(69 citation statements)

References 30 publications

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“…The hypoactivity observed on the first day of testing differs from the majority of previous studies, representing a variety of routes of administration and doses of nicotine, which showed either no effect or an increase in locomotor activity in rodents prenatally exposed to nicotine (Ajarem and Ahmad 1998;Fung 1988;Vaglenova et al 2004). However, one study (Peters and Tang 1982) found that prenatal oral administration of nicotine (6.0 mg/kg/day) via drinking water resulted in offspring that exhibited hypoactivity in an open field in the first five minutes of the session, which is quite consistent with the present findings.…”

Section: Discussioncontrasting

confidence: 92%

“…In addition, Vaglenova et al (2004) found that rats prenatally exposed to nicotine exhibited decreased entries and time spent in the open arms of an elevated-plus maze. However, one study in mice found that prenatal nicotine exposure had the opposite effect in the elevated-plus maze (Ajarem and Ahmad 1998). Moreover, Peters and Tang (1982) found that in rats prenatally exposed to nicotine that exhibited hypoactivity in an open field, neither the plasma corticosterone response to stress nor the hypothalamic norepinephrine level was significantly affected.…”

Section: Discussionmentioning

confidence: 99%

“…Numerous studies have shown a wide range of behavioral impairments in rodents prenatally exposed to nicotine, including impaired performance in the radial arm maze and Morris water maze (Levin et al 1993;Sorenson et al 1991;Yanai et al 1992), lower response and reinforcement rates under operant schedules of food delivery (Martin and Becker 1971), poorer operant discrimination performance (Martin and Becker 1971), and reduced pre-pulse inhibition of acoustic startle response . Although several animal studies have found that offspring prenatally exposed to nicotine can also exhibit hyperactivity (Ajarem and Ahmad 1998;Fung and Lau 1989;Martin and Becker 1970;Peters et al 1979;Vaglenova et al 2004), other studies have reported conflicting results (see Table 1). Some studies report hyperactivity in only a subset of rats (less than 20%), with no significant overall effect of prenatal nicotine exposure (Richardson and Tizabi 1994;Tizabi et al 1997).…”

Section: Introductionmentioning

confidence: 99%

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Effects of maternal intravenous nicotine administration on locomotor behavior in pre-weanling rats

LeSage

Gustaf

Dufek

et al. 2006

Pharmacology Biochemistry and Behavior

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Maternal tobacco use is associated with adverse developmental outcomes in offspring, including hyperactivity. Animal studies attempting to model this phenomenon have primarily used continuous s.c. nicotine infusion as the method of nicotine administration, which does not model the intermittent bolus delivery of nicotine associated with smoking in humans. The purpose of the present experiment was to examine the locomotor activity of pre-weanling offspring of pregnant rats exposed to an i.v. nicotine dosing protocol that approximates the pattern of nicotine exposure in moderate to heavy smokers. Pregnant rats were administered an i.v. bolus of 0.03 mg/kg nicotine (N=13) or saline (N=10) every 14 min for 16 hr/day, resulting in a total daily dose of 2 mg/kg (base), from gestational day 4 to delivery. Pups from each litter were tested for spontaneous locomotor activity on postnatal days (PND) 19-21 and nicotine-induced locomotor activity on PND 22. Mean birth weight was significantly lower in nicotine-exposed pups compared to controls, but body weights were equivalent between groups by the time of behavioral testing. Mean total distance traveled, vertical counts, and stereotypy counts were lower on PND 19 in nicotine-exposed pups compared to controls, but only the difference in mean stereotypy counts was statistically significant. Within session analysis revealed that both distance traveled and stereotypy were significantly decreased in nicotine-exposed pups in the first five minutes of the session on PND 19. Total time spent in the center of the field was also lower in nicotine exposed pups. Nicotine-induced increases in activity on PND 22 did not differ according to gestational exposure. These findings demonstrate that prenatal nicotine exposure in a model that mimics the pattern of nicotine exposure from cigarette smoking in humans results in offspring that exhibit low birth weight and hypoactivity in a novel environment.

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Section: Discussioncontrasting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effects of maternal intravenous nicotine administration on locomotor behavior in pre-weanling rats

LeSage

Gustaf

Dufek

et al. 2006

Pharmacology Biochemistry and Behavior

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“…Animal studies have tried to link prenatal nicotine exposure to cognitive deficits, but with limited success (Cutler et al, 1996;Ajarem and Ahmad, 1998;Ankarberg et al, 2001;AbdelRahman et al, 2005). Two late developing brain structures, the hippocampus and the cerebellum, are associated with cognitive functions.…”

Section: Introductionmentioning

confidence: 99%

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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“…,Pliszka et al, 1996,Castellanos, 1997. In animal studies, maternal nicotine exposure produces sexdependent alterations in the development of DA neurochemical markers (Fung, 1988,Fung, 1989,Ribary and Lichtensteiger, 1989,Lichtensteiger and Schlumpf, 1993,Muneoka et al, 1997, and induces hyperactivity in the offspring, which is believed to result from alterations in mesolimbic and nigrostriatal DA systems ,Fung and Lau, 1989,Richardson and Tizabi, 1994,Tizabi et al, 1997,Ajarem and Ahmad, 1998. However, one point of intense controversy is whether the actions of nicotine are mediated directly on DA neurons or are the result of indirect effects such as hypoxia (Slotkin, 1998).…”

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confidence: 99%

Developmental regulation of nicotinic acetylcholine receptors within midbrain dopamine neurons

2007

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We have combined anatomical and functional methodologies to provide a comprehensive analysis of the properties of nicotinic acetylcholine receptors (nAChRs) on developing dopamine (DA) neurons. Double-labeling in situ hybridization was used to examine the expression of nAChR subunit mRNAs within developing midbrain DA neurons. As brain maturation progressed there was a change in the pattern of subunit mRNA expression within DA neurons, such that α3 and α4 subunits declined and α6 mRNA increased. Although there were strong similarities in subunit mRNA expression in substantia nigra (SNc) and ventral tegmental area (VTA), there was higher expression of α4 mRNA in SNc than VTA at gestational day (G)15, and of α5, α6 and β3 mRNAs during postnatal development. Using a superfusion neurotransmitter release paradigm to functionally characterize nicotine-stimulated release of [ 3 H]DA from striatal slices, the properties of the nAChRs on DA terminals were also found to change with age. Functional nAChRs were detected on striatal terminals at G18. There was a decrease in maximal release in the first postnatal week, followed by an increase in nicotine efficacy and potency during the second and third postnatal weeks. In the transition from adolescence (postnatal days (P) 30 and 40) to adulthood, there was a complex pattern of functional maturation of nAChRs in ventral, but not dorsal, striatum. In males, but not females, there were significant changes in both nicotine potency and efficacy during this developmental period. These findings suggest that nAChRs may play critical functional roles throughout DA neuronal maturation. Keywords adolescent; fetal; nicotine; sex; striatum; maternal smoking Maternal smoking during pregnancy has been correlated with a number of adverse outcomes in the offspring (Lichtensteiger et al., 1988,Lichtensteiger andSchlumpf, 1993), including cognitive deficits that are often manifested in early childhood as attention deficit hyperactivity disorder (ADHD) (Millberger et al., 1996). Though the underlying neurobiological mechanism * Correspondence to: Dr. Layla Azam Department of Biology, University of Utah 257 South 1400 East Salt Lake City, UT 84112 Tel.: (801) Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. ,Pliszka et al., 1996,Castellanos, 1997. In animal studies, maternal nicotine exposure produces sexdependent alterations in the development of DA neurochemical markers (Fung, 1988,Fung, 1989,Ribary and Lichtensteiger, 1989,Lichtensteiger and Schlumpf, 1993,Muneoka et al., 1997, and induces hyperactivity in the offspring, which is believed...

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Prenatal Nicotine Exposure Modifies Behavior of Mice Through Early Development

Cited by 113 publications

References 30 publications

Effects of maternal intravenous nicotine administration on locomotor behavior in pre-weanling rats

Effects of maternal intravenous nicotine administration on locomotor behavior in pre-weanling rats

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

Developmental regulation of nicotinic acetylcholine receptors within midbrain dopamine neurons

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