Adolescent Drug Exposure and Adult PFC Function

描述(申请人提供)：青春期大脑仍在发育中，极易受到化学物质的影响。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、化学物质或疾病的不利影响。对仍在发育和修剪神经元连接的大脑的任何化学影响都可能影响这一过程，并改变本应是大脑成年命运的进程。由于正在进行的发育过程，青少年吸毒可能产生比成人吸毒严重得多的后果。 在行为学和分子分析中，我们将检验青春期大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。 PFC在早期发育和成年期的认知过程中是至关重要的。多巴胺在PFC和这些认知能力的发展中起着重要的作用。在青春期，通过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影响。在两个特定的目标中，我们计划解决在青春期接触可卡因对(1)PFC特异性测试，注意力定势转移任务，以及(2)对PFC两个区域的成人基因表达模式的潜在长期影响。这两个具体目标将在结束可卡因狂欢范例后十天，以及在成年后结束可卡因使用三周和六周后进行。在服用可卡因期间也将进行分子分析。 我们预计，在服用可卡因后很长一段时间内，PFC功能和生物学都会发生变化。如果这一范例被证明是对青少年可卡因使用的预测，我们将在未来的提案中调查青少年使用可卡因对与药物滥用相关的其他行为和大脑区域的影响。

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.