首页> 外文期刊>The European Journal of Neuroscience >Gestational nicotine exposure reduces nicotinic cholinergic receptor (nAChR) expression in dopaminergic brain regions of adolescent rats.
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Gestational nicotine exposure reduces nicotinic cholinergic receptor (nAChR) expression in dopaminergic brain regions of adolescent rats.

机译:妊娠期尼古丁暴露会降低青春期大鼠多巴胺能脑区域的烟碱胆碱能受体(nAChR)表达。

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Children of women who smoked during pregnancy are at increased risk of dependence when smoking is initiated during adolescence. We previously reported that gestational nicotine exposure attenuated dopamine release induced by nicotine delivered during adolescence. In this study, we determined the effects of gestational nicotine exposure on nicotinic cholinergic receptor (nAChR) expression. Timed pregnant rats received nicotine (2 mg/kg/day) or vehicle via mini-osmotic pumps during gestation. Treatments continued in pups via maternal nursing during postnatal days (PN) 2-14 (equivalent to the human in utero third trimester). On PN35, (125)I-epibatidine binding to nAChR was measured. The B(max) values (fmol/mg) in prefrontal cortex (PFC), nucleus accumbens (NAcc), substantia nigra (SN) and ventral tegmental area (VTA) were reduced by 26.6% (P < 0.05), 32.6% (P < 0.01), 23.0% (P < 0.01) and 27.6% (P < 0.05), respectively. In addition, gender differences were found in vehicle-treated groups; in SN and VTA, females were 79.3% (P < 0.005) and 82.9% (P = 0.08) of males, respectively. The expression of nAChR subunit mRNAs was measured using real-time RT-PCR on laser-capture microdissected tissues. In adolescent VTA, gestational nicotine exposure reduced (P < 0.05) nAChR subunit mRNAs encoding alpha3 (53.0%), alpha4 (23.9%), alpha5 (46.7%) and beta4 (61.4%). In NAcc core, the treatment increased alpha3 mRNA (75.8%). In addition, the number of neurons in VTA was reduced by 15.0% (P < 0.001). These studies indicate that gestational exposure to nicotine induces long-lasting changes in nAChR expression that may underlie the vulnerability of adolescents to dependence on nicotine.
机译:怀孕期间吸烟的妇女的孩子在青春期开始吸烟时有依赖性的风险增加。我们先前曾报道妊娠期尼古丁暴露减弱了青春期输送的尼古丁引起的多巴胺释放。在这项研究中,我们确定了妊娠烟碱暴露对烟碱胆碱能受体(nAChR)表达的影响。定时妊娠的大鼠在妊娠期间通过小型渗透泵接受了尼古丁(2 mg / kg /天)或赋形剂。在产后几天(PN)2-14(相当于子宫中期的人),通过产妇护理继续对幼崽进行治疗。在PN35上,测量了与nAChR结合的(125)I-表哌啶。前额叶皮层(PFC),伏隔核(NAcc),黑质(SN)和腹侧被盖区(VTA)的B(max)值分别降低了26.6%(P <0.05),32.6%( P <0.01),23.0%(P <0.01)和27.6%(P <0.05)。此外,在接受车辆治疗的人群中发现了性别差异。在SN和VTA中,女性分别为男性的79.3%(P <0.005)和82.9%(P = 0.08)。 nAChR亚基mRNA的表达是使用实时RT-PCR在激光捕获的显微组织上测量的。在青春期VTA中,妊娠烟碱暴露减少(P <0.05)编码α3(53.0%),α4(23.9%),α5(46.7%)和beta4(61.4%)的nAChR亚基mRNA。在NAcc核心,治疗增加了α3mRNA(75.8%)。此外,VTA中的神经元数量减少了15.0%(P <0.001)。这些研究表明,妊娠暴露于尼古丁会引起nAChR表达的长期变化,这可能是青少年容易依赖尼古丁的基础。

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