Slotkin Theodore A, Cousins Mandy M, Seidler Frederic J
Box 3813 DUMC, Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.
Brain Res. 2004 Dec 24;1030(1):159-63. doi: 10.1016/j.brainres.2004.10.009.
Alpha 7 Nicotinic acetylcholine receptors (nAChRs) play a role in axonogenesis, synaptogenesis and synaptic plasticity, and are therefore targets for developmental neurotoxicants. We administered nicotine to adolescent rats and evaluated the effects on alpha 7 nAChRs in the striatum, brainstem and cerebellum. During the period of nicotine administration (30-47.5 days of age), nicotine elicited alpha 7 nAChR upregulation with a regional hierarchy of striatum>brainstem>cerebellum. Values returned to normal or became slightly subnormal almost immediately after the cessation of treatment (50 days of age) with no further changes through 75 days of age. The temporal and regional patterns of the effects on alpha 7 nAChRs were distinct from those reported earlier for the alpha 4 beta 2 subtype, and neither adult nor fetal/neonatal administration upregulates the alpha 7 subtype in the striatum. Targeting of the striatum is thus unique to nicotine exposure during adolescence and parallels earlier work showing regionally selective effects of this treatment on synaptic signaling. We obtained preliminary evidence for nicotine-induced oxidative stress as a potential contributory mechanism. The present findings reinforce the concept of biologically distinct effects of nicotine in the adolescent brain and provide evidence for a mechanistic involvement of alpha 7 nAChRs in its unique effects during this developmental period.
α7烟碱型乙酰胆碱受体（nAChRs）在轴突发生、突触发生和突触可塑性中发挥作用，因此是发育性神经毒物的作用靶点。我们给青春期大鼠施用尼古丁，并评估其对纹状体、脑干和小脑中α7 nAChRs的影响。在尼古丁给药期间（30 - 47.5日龄），尼古丁引起α7 nAChR上调，其区域分级为纹状体>脑干>小脑。在停止治疗（50日龄）后，数值几乎立即恢复正常或略低于正常水平，直至75日龄都没有进一步变化。对α7 nAChRs影响的时间和区域模式与先前报道的α4β2亚型不同，无论是成年期给药还是胎儿/新生儿期给药都不会使纹状体中的α7亚型上调。因此，纹状体靶向作用是青春期尼古丁暴露所特有的，这与早期研究结果一致，即该治疗对突触信号传导具有区域选择性影响。我们获得了初步证据，表明尼古丁诱导的氧化应激可能是一种促成机制。本研究结果强化了尼古丁在青春期大脑中具有生物学上不同效应的概念，并为α7 nAChRs在这一发育阶段的独特效应中发挥机制性作用提供了证据。
