Prenatal exposure of rats to nicotine causes persistent alterations of nicotinic cholinergic receptors.
Prenatal exposure of rats to nicotine causes persistent alterations of nicotinic cholinergic receptors.
复制标题
DOI：
10.1016/j.brainres.2008.10.076
复制
发表时间：
2009-01-23
期刊：
影响因子：
2.9
通讯作者：
Perry DC
中科院分区：
文献类型：
--
作者：
Gold AB;Keller AB;Perry DC
我们研究了从妊娠第3天到出生后第10天（PN10）产前尼古丁暴露导致雄性大鼠大脑皮层、丘脑和纹状体nachr的即时和持续变化，以及这种暴露如何影响青少年对随后尼古丁挑战的反应。通过[3H]依比替丁结合评估受体数量，通过乙酰胆碱刺激的86Rb外排（大脑皮层和丘脑）和尼古丁刺激的多巴胺释放（纹状体）测量受体功能。产前尼古丁的直接影响，在PN10动物中评估，没有检测到任何参数。在随后的14天的青春期尼古丁暴露中发现了由产前尼古丁暴露引起的持续变化。青少年尼古丁暴露导致这三个区域的结合上调；然而，这种上调在产前暴露于尼古丁的动物的丘脑中消失了。青少年尼古丁暴露导致纹状体中尼古丁刺激的多巴胺释放减少；这种效应在产前暴露于尼古丁的动物中也消失了。PN10和PN42大鼠的参数比较揭示了中枢神经系统胆碱能系统的发育变化。在丘脑中，随着年龄的增长，结合增加，对乙酰胆碱高度敏感的86Rb外排比例也增加。在皮质中，结合也随着年龄的增长而增加，但86Rb的总流出量没有变化，高敏感性流出量与低敏感性流出量的比例随年龄的增长而下降。尼古丁刺激的纹状体多巴胺释放（包括总释放和α- concontoxin mii抗性释放）在naïve动物中随着年龄的增长而增加，但在产前暴露于尼古丁的动物中没有。这些发现表明，产前暴露于尼古丁会导致尼古丁对nachr的调节发生变化，这种变化会持续到青春期。这些变化可能在吸烟母亲的青少年后代中观察到的尼古丁成瘾风险增加中起作用。
We examined for immediate and persistent changes in nAChRs in cerebral cortex, thalamus and striatum of male rats caused by prenatal exposure to nicotine from gestational day 3 to postnatal day 10 (PN10), and how such exposure affected the responses of adolescents to subsequent nicotine challenge. Receptor numbers were assessed by [3H]epibatidine binding and receptor function was measured by acetylcholine-stimulated 86Rb efflux (cerebral cortex and thalamus) and nicotine-stimulated dopamine release (striatum). Immediate effects of prenatal nicotine, assessed in PN10 animals, were not detected for any parameter. A subsequent 14 day nicotine exposure in adolescence revealed persistent changes caused by prenatal nicotine exposure. Nicotine exposure in adolescents caused up-regulation of binding in all three regions; however, this up-regulation was lost in thalamus from animals prenatally exposed to nicotine. Nicotine exposure in adolescents caused decreased nicotine-stimulated dopamine release in striatum; this effect was also lost in animals prenatally exposed to nicotine. Comparison of parameters in PN10 and PN42 rats revealed developmental changes in the CNS cholinergic system. In thalamus, binding increased with age, as did the proportion of 86Rb efflux with high sensitivity to acetylcholine. In cortex, binding also increased with age, but there was no change in total 86Rb efflux, and the proportion of high to low sensitivity efflux declined with age. Nicotine-stimulated striatal dopamine release (both total and α-conotoxin MII-resistant release) increased with age in naïve animals, but not in those prenatally exposed to nicotine. These findings demonstrate that prenatal exposure to nicotine causes alterations in the regulation of nAChRs by nicotine that persist into adolescence. These changes may play a role in the increased risk for nicotine addiction observed in adolescent offspring of smoking mothers.
登录
查看更多内容
DOI：
10.1124/jpet.301.2.651
发表时间：
2002-05-01
影响因子：
3.5
作者：
Grady, SR;Murphy, KL;Collins, AC
通讯作者：
Collins, AC
影响因子：
4.7
作者：
Marks, MJ;Rowell, PP;Collins, AC
通讯作者：
Collins, AC
影响因子：
3.6
作者：
Gotti, Cecilia;Moretti, Milena;Marks, Michael J.
通讯作者：
Marks, Michael J.
影响因子：
3.6
作者：
Briggs, CA;Gubbins, EJ;Surowy, CS
通讯作者：
Surowy, CS
影响因子：
3.6
作者：
Moroni, Mirko;Zwart, Ruud;Bermudez, Isabel
通讯作者：
Bermudez, Isabel