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大鼠青春期尼古丁暴露导致的长期认知缺陷。

Long-lasting cognitive deficits resulting from adolescent nicotine exposure in rats.

作者信息

Counotte Danielle S, Spijker Sabine, Van de Burgwal Linda H, Hogenboom François, Schoffelmeer Anton N M, De Vries Taco J, Smit August B, Pattij Tommy

机构信息

Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Vrije Universiteit, Amsterdam, The Netherlands.

出版信息

Neuropsychopharmacology. 2009 Jan;34(2):299-306. doi: 10.1038/npp.2008.96. Epub 2008 Jun 25.

Abstract

Adolescence is a developmental period, during which the brain and particularly medial prefrontal cortical (mPFC) regions thereof have not fully matured. Because epidemiological data have suggested that adolescent nicotine use may result in disturbances in cognitive function in adulthood, we investigated the long-term effects of adolescent nicotine exposure in rats. Male Wistar rats were exposed to either nicotine (three times daily, 0.4 mg/kg s.c.) or saline for 10 days during (postnatal day (PND) 34-43) or following (PND 60-69) adolescence. After 5 weeks during adulthood, separate groups of animals were tested in operant paradigms taxing attention and distinct measures of impulsivity. Visuospatial attention and impulsive action were tested in the five-choice serial reaction time task, whereas impulsive choice was assessed in the delayed reward task. Our data show that adolescent, but not postadolescent, nicotine exposure affects cognitive performance in adulthood and results in diminished attentional performance and increments in impulsive action, while leaving impulsive choice intact. This altered cognitive performance appeared to be associated with enhanced releasability of dopamine in the mPFC. Together, these data suggest that adolescence is a time window during which the brain is vulnerable to long-lasting cognitive disturbances resulting from nicotine exposure.

摘要

青春期是一个发育阶段,在此期间大脑尤其是内侧前额叶皮质(mPFC)区域尚未完全成熟。由于流行病学数据表明青少年使用尼古丁可能会导致成年期认知功能障碍,我们研究了青少年尼古丁暴露对大鼠的长期影响。雄性Wistar大鼠在青春期期间(出生后第34 - 43天)或之后(出生后第60 - 69天)接受尼古丁(每天3次,皮下注射0.4mg/kg)或生理盐水注射,持续10天。成年期5周后,对不同组的动物进行操作范式测试,以评估注意力和不同的冲动性指标。在五选择连续反应时任务中测试视觉空间注意力和冲动行为,而在延迟奖励任务中评估冲动选择。我们的数据表明,青少年期而非青春期后尼古丁暴露会影响成年期的认知表现,导致注意力表现下降和冲动行为增加,而冲动选择不受影响。这种改变的认知表现似乎与mPFC中多巴胺释放能力增强有关。总之,这些数据表明青春期是一个时间窗口,在此期间大脑易受尼古丁暴露导致的长期认知障碍影响。

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