Adolescent Drug Exposure and Adult PFC Function

描述（由申请人提供）：青少年的大脑仍处于发育阶段，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大人，他们更容易受到药物、化学品或疾病的不利影响。任何化学物质对仍在发育和修剪神经元连接的大脑的影响都可能影响这一过程，并改变本应是成年人大脑命运的进程。由于持续的发育过程，青少年药物接触可能比成人药物接触产生更严重的后果。

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.