Adolescent Cocaine Abuse: Electrophysiology & Behavior

青少年可卡因滥用：电生理学

基本信息

批准号：
7467333
负责人：
Michela Marinelli
金额：
$ 28.99万
依托单位：
ROSALIND FRANKLIN UNIV OF MEDICINE & SCI
依托单位国家：
美国
项目类别：
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/7467333
关键词：
Action Potentials Adolescence Adolescent Adult Affect Age Autoreceptors Behavior Behavioral Behavioral Model Brain Cell physiology Cells Cocaine Cocaine Abuse Cocaine Dependence Condition Development Dopamine Drug Exposure Electrophysiology (science)Excitatory Synapse Exhibits Exposure to Goals Human In Vitro Individual Injection of therapeutic agent Light Mediating Midbrain structure Motivation Nature Neurons Pharmaceutical Preparations Play Predisposition Prevention Probability Procedures Property Rattus Regulation Research Personnel Rewards Risk Rodent Model Role Running Sampling Self Administration Self-Administered Severities Synapses Techniques Testing Translating addiction adolescent drug use age related behavior test dopamine system dopaminergic neuron early onset in vivo insight interdisciplinary approach neuroadaptation neurochemistry neurophysiology programs psychostimulant recreational drug use research study response therapeutic target

项目摘要

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对精神刺激药物的敏感性更高，并且增加了成瘾的风险。这种对药物自我给药的敏感性增加可能是由于青少年大脑反应或适应与成人大脑相比反复暴露的药物的差异。该提案的总体目标是使用啮齿动物模型了解有助于对可卡因自我管理的青少年敏感性的神经生理和行为决定因素。多巴胺系统将是这些研究的重点，因为它在介导上瘾的药物的有益作用中起着核心作用。具体目的是：确定青春期是否具有多巴胺细胞的兴奋性升高，以及这些神经元的固有抑制特性降低（AIM 1）和/或增加对这些细胞的兴奋性突触输入增加（AIM 2）。 AIM 3将确定多巴胺神经元功能的变化是否转化为可卡因自我管理行为的差异。在这些目标中，将在重复可卡因暴露之前和之后比较青少年和成年大鼠，以评估个体是否表现出固有的差异和/或显示出可卡因诱导的神经适应性差异，以促进自我管理行为。神经元活性将使用体内和体外电生理技术评估；行为测试将包括各种自我管理程序，这些程序允许估计可卡因的奖励作用和自我管理药物的动机。总体而言，使用多学科方法，该提案将检查从细胞到行为水平，在可卡因自我管理中的青少年/成人差异的潜在机制。这些研究将使用与人类条件相关的行为模型，以洞悉青少年药物使用的原因和影响。从长远来看，这些发现将有助于开发新的有针对性的治疗策略，以治疗或预防可卡因成瘾。