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：
8213527
负责人：
Sean Bjorn Ostlund
金额：
$ 30.15万
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/8213527
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 public health relevance 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）：人们越来越关注滥用药物破坏正常学习和决策过程的可能性，从而导致强迫性、病态的药物寻求行为的发展。长期接触可卡因等精神兴奋剂，会导致黑质纹状体和中脑边缘多巴胺通路变得敏感，这些通路对于习惯的养成（即，僵化的、刺激相关的反应）和激励动机的表达（即，与奖励相关的线索，以促进食欲行为，或诱发“想要”）。在这个项目中，我们将评估两种不同的（但不是相互排斥的）成瘾理论：药物暴露使习惯主导对行为选择的控制（以牺牲深思熟虑的、目标导向的行为选择为代价），并且药物暴露增强了对行为选择的控制。与奖励相关的环境线索对绩效的影响。我们的计划是结合使用仔细控制的行为程序和完善的神经化学检测技术来回答以下问题：（i）器乐训练期间多巴胺的释放是否与假设负责的基于预测误差的强化信号的分布相匹配控制习惯的形成？ (ii) 预接触可卡因对习惯性表现的获得和表达以及与强化相关的多巴胺信号传导有何影响？ (iii) 中脑边缘多巴胺流出是否介导了指导基于线索的行动选择的激励过程？ (iv) 以及，重复接触可卡因对基于线索的行动选择和中脑边缘多巴胺对奖励相关线索的反应有何影响？最近的研究表明，与非偶然性可卡因相比，与反应相关的可卡因会引发更强的神经化学作用，并导致多巴胺释放的回路发生更显着和更持久的变化。这些发现对评估实验者施用的药物对学习、行为控制和大脑化学的影响的研究的有效性提出了质疑。因此，本申请的次要目标是确定重复接触可卡因的行为和神经化学效应是否取决于药物输送模式。公共卫生相关性：反复接触滥用药物，包括可卡因等精神兴奋剂，可以显着改变支持学习和决策的神经回路。现代成瘾理论认为，这些改变导致了成瘾者表现出的强迫性、病态的药物寻求行为。当前的应用程序将完善的行为测试与神经化学分析相结合，以研究服用可卡因如何影响生物体获取和选择行为的方式。