Project 2: Individual Variation in Dopamine Transmission and Attribution of Incen

项目 2：多巴胺传递的个体差异和燃烧的归因

• 批准号: 8638914
• 负责人: Brandon Aragona
• 金额: $ 26.74万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8638914
• 关键词: Abstinence; Address; Animals; Association Learning; Behavior; Breeding; Cocaine; Cues; Data; Development; Disease; Dopamine; Drug Addiction; Excision; Extinction (Psychology); Food; Frequencies; Goals; Human; Incentives; Individual; Individual Differences; Instruction; Intake; Learning; Maintenance; Measurement; Measures; Motivation; Neurobiology; Neurosciences; Nucleus Accumbens; Pathway interactions; Pharmaceutical Preparations; Phenotype; Positron-Emission Tomography; Pre-Clinical Model; Predictive Value; Predisposition; Property; Public Health; Rattus; Relapse; Relative (related person); Rewards; Rodent; Role; Scanning; Self Administration; Signal Pathway; Signal Transduction; Specificity; Staging; Stimulus; System; Technology; Testing; Time; United States; Variant; Work; addiction; animal breeding; base; classical conditioning; conditioning; drug addict; drug seeking behavior; extracellular; learned behavior; motivated behavior; novel; preclinical study; relating to nervous system; research study; response; therapy development; transmission process; uptake; willingness

PROJECT SUMMARY (See instructions): One of the primary challenges with the treatment of dmg addiction is that most drug addicts are not able to refrain from taking drugs even though they desperately wish to quit, frequently relapsing even after long periods of abstinence. One powerful trigger for relapse is the presentation of environmental stimuli that were previously associated with drug taking (i.e., a drug-associated cues). Most importantly for this proposal, there is significant individual variation in the degree to which presentation of a drug-associated cue increases the incentive motivation to take drugs. Moreover, the degree that such cues increase the desire to take drug is correlated with how much the cue increases dopamine (DA) transmission, both in PET studies in humans and in preclinical studies in rats. Therefore, rodent studies can be used to study the relationship between the incentive value of drug-cues and DA signaling. In the current application, we propose to measure subsecond changes in DA concentration in freely moving rats and examine the relationship between phasic DA transmission and individual variation in the propensity to attribute incentive value to reward-predictive cues, especially drug-cues. This technology, fast-scan cyclic voltammetry (FSCV), can distinguish between specific aspects of DA transmission (such as release and uptake) and has been used to reveal novel neural consequences of cocaine intake and regional specificity associated with cue-cocaine conditioning. Here, we will use FSCV to determine if there are inherent differences in DA signaling pathways that predict individual variation in the propensity to attribute incentive value to reward-cues. We will then determine how incentive motivation impacts increased DA transmission by reward-predictive cues (including drug-associated cues) and how this is related to individual differences in drug-seeking and relapse. Given the enormous variation in the susceptibility to develop addiction, understanding the neurobiological basis of this susceptibility is critical for treatment of the disease.

项目概述（见说明）：