Altered attention and prefrontal cortex gene expression in rats after binge-like exposure to cocaine during adolescence
Altered attention and prefrontal cortex gene expression in rats after binge-like exposure to cocaine during adolescence
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DOI：
10.1523/jneurosci.2391-06.2006
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发表时间：
2006-09-20
影响因子：
5.3
通讯作者：
Konradi, Christine
中科院分区：
文献类型：
--
作者：
Black, Yolanda D.;Maclaren, Fair R.;Konradi, Christine
非法使用药物往往在青春期开始并逐步升级，造成长期的不良后果。由于越来越多的人认为神经发育会持续到青春期，成瘾研究越来越多地投资于了解早期暴露于滥用药物的行为和分子后果。在一个新的狂欢管理模式，旨在模拟人类青少年药物使用的模式，我们管理递增剂量的可卡因或生理盐水在12天的发育期[出生后第35天（P35）至P46]对应的人类青春期。在成年期（P70），用这种方案治疗的大鼠对可卡因的刺激作用表现出更高的反应性。成年大鼠在执行注意力转移任务时也表现出异常快速的注意力转移，该任务测量在刺激之间转移注意力的能力，并且其表现需要完整的前额叶皮层（PFC）。在青春期用可卡因治疗也引起PFC内编码细胞粘附分子和转录因子的基因表达的急性改变。此外，我们观察到组蛋白甲基化的减少，这可能表明在所观察到的基因表达模式的变化中染色质重塑的作用。这些发现表明，在青春期接触可卡因对大鼠PFC具有深远的分子和行为后果，这些后果随着时间的推移而发展，并在药物给药停止后持续很长时间。
Illicit use of drugs frequently begins and escalates during adolescence, with long-term adverse consequences. Because it is increasingly accepted that neural development continues through adolescence, addiction research has become more invested in understanding the behavioral and molecular consequences of early exposure to drugs of abuse. In a novel binge administration paradigm designed to model the pattern of human adolescent drug use, we administered ascending doses of cocaine or saline during a 12-d developmental period [ postnatal day 35 ( P35) to P46] corresponding to human adolescence. During adulthood (P70), rats treated with this regimen displayed increased responsiveness to the stimulant effects of cocaine. Adult rats also displayed abnormally rapid shifts in attention when performing an attentional set-shifting task, which measures the ability to shift attention between stimuli and whose performance requires an intact prefrontal cortex (PFC). Treatment with cocaine during adolescence also caused acute alterations in the expression of genes encoding cell adhesion molecules and transcription factors within the PFC. Furthermore, we observed decreases in histone methylation, which may indicate a role for chromatin remodeling in the observed changes in gene expression patterns. These findings suggest that exposure to cocaine during adolescence has far-reaching molecular and behavioral consequences in the rat PFC that develop over time and endure long after drug administration has ceased.