Cocaine-Seeking and the Transfer of Behavioral Control

可卡因寻求与行为控制的转移

基本信息

批准号：
8041548
负责人：
Sean Bjorn Ostlund
金额：
$ 29.94万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-02-01 至 2015-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8041548
关键词：
Address Affect Appetitive Behavior Behavior Behavior Control Behavioral Binding Biological Assay Brain Brain Chemistry Cells Characteristics Chronic Cocaine Computer Simulation Corpus striatum structure Cues Decision Making Detection Development Dopamine Dorsal Drug Delivery Systems Drug Exposure Drug abuse Drug usage Exposure to Food Goals Habits Incentives Knowledge Lead Learning Location Mediating Microdialysis Motivation Nature Nucleus Accumbens Operant Conditioning Organism Outcome Pathway interactions Performance Pharmaceutical Preparations Physiological Procedures Process Psychological reinforcement Rattus Reporting Response to stimulus physiology Rewards Rodent Role Scanning Signal Transduction Site Stimulus System Techniques Testing Training addiction base behavior test cocaine exposure cost drug of abuse drug seeking behavior habit learning in vivo interest motivational processes neuroadaptation neurochemistry neuromechanism paired stimuli psychostimulant response theories

项目摘要

DESCRIPTION (provided by applicant): There is growing interest in the possibility that drugs of abuse subvert normal learning and decision- making processes, leading to the development of compulsive, pathological drug-seeking behavior. Chronic exposure to psychostimulants, like cocaine, results in sensitization of nigrostriatal and mesolimbic dopamine pathways, which are critically involved in the acquisition of habits (i.e., rigid, stimulus-bound responses) and the expression of incentive motivation (i.e., the capacity for a reward-related cue to facilitate appetitive behaviors, or induce 'wanting'). In this project, we will evaluate two distinct (but not mutually exclusive) theories of addiction: that drug exposure allows habits to dominate the control of action selection (at the expense of deliberative, goal-directed action selection), and that drug exposure potentiates the influence of reward-related environmental cues over performance. Our plan is to use a combination of carefully controlled behavioral procedures and well-established neurochemical detection techniques to answer the following questions: (i) Does dopamine release during instrumental training match the profile of the prediction error-based reinforcement signal assumed to be responsible for governing habit formation? (ii) What are the effects of cocaine pre-exposure on the acquisition and expression of habitual performance and on reinforcement-related dopamine signaling? (iii) Does mesolimbic dopamine efflux mediate the incentive motivational processes that guide cue-based action selection? (iv) and, What are the effects of repeated cocaine exposure on cue-based action selection and on the mesolimbic dopamine response to reward-related cues? Recent studies have shown that response-contingent cocaine elicits stronger neurochemical effects and results in more dramatic and longer-lasting changes in the circuitry underlying dopamine release than noncontingent cocaine. Such findings raise questions about the validity of studies assessing the effects of experimenter-administered drugs on learning, behavioral control, and brain chemistry. Therefore, a secondary objective of the current application is to determine whether the behavioral and neurochemical effects of repeated cocaine exposure depend on the mode of drug delivery. PUBLIC HEALTH RELEVANCE: Repeated exposure to drugs of abuse, including psychostimulants like cocaine, can significantly alter the neurocircuitry that supports learning and decision-making. Modern theories of addiction propose that these alterations lead to the compulsive, pathological drug-seeking behavior displayed by addicts. The current application combines well-established behavioral tests with neurochemical analysis to investigate how taking cocaine influences the way organisms acquire and select actions.

描述（由申请人提供）：对滥用药物颠覆正常学习和决策过程的可能性越来越兴趣，从而导致强迫性，病理性的毒品寻求毒品行为的发展。 Chronic exposure to psychostimulants, like cocaine, results in sensitization of nigrostriatal and mesolimbic dopamine pathways, which are critically involved in the acquisition of habits (i.e., rigid, stimulus-bound responses) and the expression of incentive motivation (i.e., the capacity for a reward-related cue to facilitate appetitive behaviors, or induce 'wanting').在这个项目中，我们将评估成瘾的两种不同（但不是相互排斥的）理论：该药物暴露允许习惯主导行动选择的控制（以审议性，目标指导的行动选择为代价），并且该药物暴露增强了与奖励相关环境线索对性能的影响。我们的计划是结合仔细控制的行为程序和良好的神经化学检测技术来回答以下问题：（i）在仪器培训期间释放多巴胺是否释放了匹配的基于预测错误的增强信号的概况，假定基于错误的习惯形成习惯？（ii）可卡因预曝光对习惯性能的获取和表达以及与增强相关的多巴胺信号传导有什么影响？（iii）中断多巴胺外排能否介导指导基于提示的动作选择的激励动机过程？（iv），并且，重复可卡因暴露对基于提示的作用选择以及中唇多巴胺对与奖励相关的提示的反应有什么影响？最近的研究表明，可卡因的反应可卡因会引起更强的神经化学作用，并导致多巴胺释放的电路的更具戏剧性和更长的变化，而不是非转化可卡因。此类发现提出了有关评估实验者管理药物对学习，行为控制和脑化学的影响的研究有效性的问题。因此，当前应用的次要目标是确定重复可卡因暴露的行为和神经化学作用是否取决于药物递送的方式。公共卫生相关性：反复接触滥用药物的药物，包括可卡因等精神刺激剂，可以显着改变支持学习和决策的神经记录。成瘾的现代理论表明，这些改变会导致成瘾者表现出的强迫性病理性毒品的行为。当前的应用将良好的行为测试与神经化学分析相结合，以研究可卡因如何影响生物体获得和选择作用的方式。