Adolescent Cocaine Abuse: Electrophysiology & Behavior

青少年可卡因滥用：电生理学

• 批准号: 7144536
• 负责人: Michela Marinelli
• 金额: $ 30.56万
• 依托单位: ROSALIND FRANKLIN UNIV OF MEDICINE & SCI
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-15 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7144536
• 关键词: behavior; cocaine; electrophysiology; neurons

DESCRIPTION (provided by applicant): There is growing concern that adolescence is associated with greater sensitivity to psychostimulant drugs and increased risk of addiction. Such increased susceptibility to drug self-administration could be due to differences in the way the adolescent brain reacts or adapts to repeated drug exposure compared with the adult brain. The overall goal of this proposal is to understand the neurophysiological and behavioral determinants that contribute to adolescent susceptibility to cocaine self-administration, using rodent models. The dopamine system will be the focus of these studies, as it plays a central role in mediating the rewarding effects of addictive drugs. The specific aims are: to determine whether adolescence is characterized by heightened excitability of dopamine cells, and whether this is mediated by decreased intrinsic inhibitory properties of these neurons (Aim 1) and/or increased excitatory synaptic input to these cells (Aim 2). Aim 3 will establish whether changes in dopamine neuron function translate into differences in cocaine self-administration behavior. Throughout these aims, adolescent and adult rats will be compared both before and after repeated cocaine exposure to appraise whether individuals exhibit inherent differences, and/or show differential cocaine- induced neuroadaptations that could facilitate self-administration behavior. Neuronal activity will be assessed using in vivo and in vitro electrophysiology techniques; behavioral tests will consist of a variety of self-administration procedures that allow estimating the rewarding effects of cocaine and motivation to self-administer the drug. Overall, using a multidisciplinary approach this proposal will examine, from the cellular to the behavioral level, potential mechanisms underlying adolescent/adult differences in cocaine self-administration. These studies will use behavioral models that are relevant to the human condition to provide insight into both the causes and effects of adolescent drug use. In the long run, these findings will facilitate the development of new targeted therapeutic strategies for the treatment or prevention of cocaine addiction.

描述（由申请人提供）：人们越来越担心青春期与精神兴奋药物的敏感性增加和成瘾风险增加有关。这种对自我给药的敏感性增加可能是由于与成人大脑相比，青少年大脑对重复药物暴露的反应或适应方式存在差异。该提案的总体目标是使用啮齿动物模型了解导致青少年对可卡因自我给药易感性的神经生理学和行为决定因素。多巴胺系统将成为这些研究的焦点，因为它在调节成瘾药物的奖赏效应中发挥着核心作用。具体目标是：确定青春期是否以多巴胺细胞兴奋性增强为特征，以及这是否是由这些神经元的内在抑制特性降低（目标 1）和/或这些细胞的兴奋性突触输入增加（目标 2）介导的。目标 3 将确定多巴胺神经元功能的变化是否会转化为可卡因自我给药行为的差异。在这些目标中，将在重复接触可卡因之前和之后对青少年和成年大鼠进行比较，以评估个体是否表现出固有差异，和/或表现出可卡因诱导的差异神经适应，从而促进自我给药行为。将使用体内和体外电生理学技术评估神经元活动；行为测试将包括各种自我给药程序，可以评估可卡因的奖励效果和自我给药的动机。总体而言，该提案将采用多学科方法，从细胞水平到行为水平，研究青少年/成人可卡因自我给药差异的潜在机制。这些研究将使用与人类状况相关的行为模型来深入了解青少年吸毒的原因和影响。从长远来看，这些发现将有助于开发新的靶向治疗策略来治疗或预防可卡因成瘾。