Adolescent Drug Exposure and Adult PFC Function

描述（由申请人提供）：青少年的大脑仍在发育，非常容易受到化学影响。 从神经生物学的角度来看，儿童和青少年不是小成年人，他们更容易受到药物，化学品或疾病的不良影响。 任何对仍在发育和修剪神经元连接的大脑的化学影响都可能影响这一过程，并改变大脑的成年命运。 由于正在进行的发育过程，青少年接触毒品可能比成人接触毒品造成严重得多的后果。 在行为和分子分析中，我们将检验青春期过量服用可卡因会影响成年期前额叶皮质（PFC）的生物学和功能的假设。 前额叶皮层对早期发育和成年期的认知过程至关重要。 多巴胺在PFC和这些认知能力的发展中起着重要作用。 在青春期使用可卡因等化学物质人为改变多巴胺水平，可能会对成年后的认知过程产生深远的影响。 在两个具体的目标，我们计划解决可卡因暴露在青春期的潜在长期影响（1）PFC特定的测试，注意力转移任务，和（2）成人基因表达模式在两个领域的PFC。这两个具体的目标将进行10天后完成可卡因狂欢范式，并在成年后3和6周后结束可卡因管理。 在可卡因给药期间也将进行分子分析。 我们预计，在可卡因给药后很长一段时间内，PFC的功能和生物学都会发生变化。 如果这种模式被证明是预测青少年可卡因管理，我们将在未来的建议，调查青少年可卡因管理的后果对其他行为和大脑区域相关的药物滥用。

DESCRIPTION (provided by applicant): The adolescent brain is still developing and highly vulnerable to chemical influences. From a neurobiological perspective, children and adolescents are not small adults, and they are more vulnerable to the adverse effects of drugs, chemicals, or diseases. Any chemical impact on a brain that is still developing and pruning neuronal connections can affect this process and alter the course of what should have been the adult destiny of the brain. By virtue of the ongoing developmental processes, adolescent drug exposure can have far more serious consequences than adult drug exposure. In a behavioral and a molecular analysis, we will test the hypothesis that binge-administration of cocaine during adolescence affects the biology and function of the prefrontal cortex (PFC) in adulthood. The PFC is critical for cognitive processing during early development and into adulthood. Dopamine plays an important role in the development of the PFC and of these cognitive abilities. An artificial alteration of dopamine levels by chemicals such as cocaine during adolescence could have a profound effect on cognitive processing in adulthood. In two specific aims we plan to address the potential long-term effect of cocaine exposure during adolescence on (1) a PFC-specific test, the attentional set-shifting task, and (2) on adult gene expression patterns in two areas of the PFC. Both specific aims will be carried out ten days after finishing the cocaine binge-paradigm, and in adulthood three and six weeks after the end of cocaine administration. Molecular analysis will also be carried out during cocaine administration. We expect to see altered PFC function and biology long after cocaine administration has seized. If this paradigm proves to be predictive of adolescent cocaine administration, we will, in future proposals, investigate the consequences of adolescent cocaine administration on other behaviors and brain areas relevant to drug abuse.