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）：青少年大脑仍在发育，非常容易受到化学影响。 从神经生物学的角度来看，儿童和青少年并不是小成年人，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会影响这一过程，并改变大脑本应成为成人的命运。 由于持续的发育过程，青少年药物暴露可能比成人药物暴露产生更严重的后果。 在行为和分子分析中，我们将检验以下假设：青春期大量服用可卡因会影响成年期前额皮质 (PFC) 的生物学和功能。 PFC 对于早期发育和成年期间的认知处理至关重要。 多巴胺在前额皮质和这些认知能力的发展中发挥着重要作用。 青春期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。 在两个具体目标中，我们计划解决青春期可卡因暴露对（1）PFC 特异性测试、注意力转移任务的潜在长期影响，以及（2）对成人两个领域的基因表达模式的潜在影响。全氟碳化物。 这两个具体目标将在完成可卡因狂饮模式十天后实现，并在成年后三周和六周后实现。 分子分析也将在可卡因给药期间进行。 我们预计在可卡因吸毒后很长一段时间内，PFC 的功能和生物学都会发生改变。 如果这种范式被证明可以预测青少年使用可卡因，我们将在未来的提案中研究青少年使用可卡因对其他行为和与药物滥用相关的大脑区域的影响。