Adolescent Drug Exposure and Adult PFC Function

青少年药物暴露与成人 PFC 功能

• 批准号: 6952446
• 负责人: CHRISTINE L KONRADI
• 金额: $ 14.24万
• 依托单位: MCLEAN HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-30 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6952446
• 关键词: animal developmental psychology; behavior test; behavioral /social science research tag; cocaine; cognition; developmental neurobiology; gene expression; gene expression profiling; juvenile animal; laboratory rat; messenger RNA; microarray technology; neurochemistry; neuropharmacology; neurophysiology; prefrontal lobe /cortex; psychopharmacology

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.

描述（由申请人提供）：青春期大脑仍在发展，并且非常容易受到化学影响的影响。 从神经生物学的角度来看，儿童和青少年不是小成年人，它们更容易受到药物，化学物质或疾病的不利影响。 对仍在发展和修剪神经元连接的大脑的任何化学影响都会影响这一过程，并改变本应成为大脑的成年命运的过程。 由于持续的发育过程，青春期药物暴露可能比成人药物暴露更严重。 在行为和分子分析中，我们将测试以下假设：青春期中可卡因的暴饮暴食会影响成年前额叶皮质（PFC）的生物学和功能。 PFC对于早期发展和成年期间的认知处理至关重要。 多巴胺在PFC和这些认知能力的发展中起着重要作用。 青春期可卡因等化学物质对多巴胺水平的人工化改变可能会对成年后的认知加工产生深远的影响。 在两个具体的目标中，我们计划解决青春期可卡因暴露在（1）PFC特异性测试，注意设置转移任务以及（2）对成人基因表达模式中的潜在长期影响。 PFC。 这两个具体目标将在结束可卡因暴饮暴食后十天，在可卡因给药结束后的三到六个星期内成年。 可卡因给药期间还将进行分子分析。 我们希望在可卡因给药抓住后很长时间会看到PFC功能和生物学的改变。 如果该范式被证明可以预测青少年可卡因给药，那么在将来的建议中，我们将研究青少年可卡因给药对其他与药物滥用有关的其他行为和大脑领域的后果。