Gestational nicotine-induced changes in adolescent neuronal activity.

Gestational nicotine-induced changes in adolescent neuronal activity.
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妊娠尼古丁引起青少年神经元活动的变化。

DOI:
10.1016/j.brainres.2006.04.001
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发表时间:
2006
期刊:
Brain research.
影响因子:
--
通讯作者:
Leslie,FrancesM
Leslie,FrancesM
中科院分区:
--
文献类型:
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作者:
Park,MinjungK;Loughlin,SandraE;Leslie,FrancesM

文献摘要

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怀孕期间吸烟与婴儿的许多生理和神经行为缺陷有关,这些缺陷会持续到青春期。为了更好地理解潜在的机制,我们用尼古丁治疗怀孕的大鼠,并评估了青春期雄性后代大脑中直接早期基因c-fos的表达,作为神经元活动的衡量标准。妊娠母鼠从妊娠第4天至妊娠第18天,分别输注尼古丁(3 mg/kg/天)或生理盐水。在G22出生后,交叉饲养幼崽,并在出生后第21天断奶。短句来源采用原位杂交技术,对p38 ~ 40岁青少年子代脑切片进行c-fos mRNA在急性注射生理盐水或尼古丁(0.03、0.1、0.3 mg/kg)后的表达进行分析。急性尼古丁刺激增加了伏隔核壳、终纹侧床核、下丘脑室旁核、外弯背核和上丘内c-fos的表达,而减少了边缘皮层前c-fos的表达。妊娠期尼古丁治疗对尼古丁引起的急性c-fos mRNA水平的改变没有影响。然而,妊娠期尼古丁处理增加了边缘下皮层和伏隔核内基底c-fos mRNA的表达。这些数据表明,妊娠期尼古丁不会引起尼古丁诱导的青少年大脑c-fos表达的全局变化。然而,妊娠期药物暴露会改变中皮质边缘结构内的基础神经元活动,这对动机行为至关重要。这些变化可能是吸烟母亲的后代在注意力、认知和冲动控制方面的一些行为缺陷的基础。
Smoking during pregnancy is associated with numerous physiological and neurobehavioral deficits in infants, which persist into adolescence. To better understand the underlying mechanisms, we have treated pregnant rats with nicotine and have evaluated expression of the immediate early gene c-fos, as a measure of neuronal activity, in the brains of adolescent male offspring. Pregnant dams were infused with nicotine (3 mg/kg/day) or saline from gestational day (G) 4 until G18. After birth on G22, litters were cross fostered and weaned at postnatal day (P) 21. Brain sections from adolescent offspring, aged P38–40, were analyzed by in situ hybridization for regional c-fos mRNA expression in response to acute injection of saline or nicotine (0.03, 0.1, 0.3 mg/kg). Acute nicotine challenge increased c-fos expression within nucleus accumbens shell, lateral bed nucleus of the stria terminalis, paraventricular nucleus of the hypothalamus, dorsal lateral geniculate, and superior colliculus, whereas c-fos expression was decreased in prelimbic cortex. There was no effect of gestational nicotine treatment on acute nicotine-induced alterations in c-fos mRNA levels. However, basal c-fos mRNA expression within infralimbic cortex and nucleus accumbens core was increased by gestational nicotine treatment. These data indicate that gestational nicotine does not produce global changes in nicotine-induced c-fos expression in adolescent brain. However, gestational drug exposure changes basal neuronal activity within mesocorticolimbic structures that are critical for motivated behavior. Such changes may underlie some of the behavioral deficits in attention, cognition, and impulse control that have been reported in the offspring of smoking mothers.