Effect of cocaine sensitization on cue-evoked reward seeking and dopamine release

可卡因致敏对线索诱发的奖励寻求和多巴胺释放的影响

• 批准号: 8458178
• 负责人: Ian Alfredo Mendez
• 金额: $ 5.22万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-01 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8458178
• 关键词: Abstinence; Affect; Behavior; Behavior Control; Behavioral; Brain; Cocaine; Control Groups; Costs and Benefits; Cues; Decision Making; Development; Dopamine; Drug Exposure; Drug usage; Employment; Environmental Impact; Euphoria; Exposure to; Family Relationship; Future; Goals; Health; Impairment; Incentives; Individual; Monitor; Motivation; Nature; Nucleus Accumbens; Pharmaceutical Preparations; Publishing; Rattus; Recording of previous events; Reporting; Research; Rewards; Role; Scanning; Self Administration; Self-Administered; Stimulus; System; Training; Withdrawal Symptom; addiction; cost; discount; discounting; dopamine system; driving behavior; drug of abuse; drug seeking behavior; extracellular; preference; psychostimulant; public health relevance; research study; response; theories; treatment effect; treatment strategy

DESCRIPTION (provided by applicant): Environmental cues associated with reward can impact actions and decisions that involve responding for rewards. The influence of environmental cues on action selection is particularly relevant to addiction, in which we see a loss of behavioral control, and increases in habitual drug seeking behavior. Presentation of reward associated cues elicits dopamine (DA) release within the nucleus accumbens (NA), an effect that is believed to underlie increases in reward seeking. The incentive sensitization theory of addiction posits that repeated psychostimulant exposure sensitizes this system, allowing stimuli to more easily activate the DA system and enhance motivation. Thus, drug exposure should allow cues paired with reward to exert greater control over behavior, explaining the sensitive nature of cue-induced drug seeking behavior in addicted individuals. The first objective of the proposed experiments will be to determine, in rats, if cocaine sensitization potentiates cue- evoked reward responding and DA release in the NA and will provide me with training in fast-scan cyclic voltammetry and the Pavlovian-to-instrumental paradigm. The association of a cost with a large reward option can decrease its value and shift choice toward a smaller, less costly reward, and addicted individuals have been repeatedly shown to be more likely to discount larger, more costly rewards, than healthy controls. Interestingly, the presence or absence of reward-related cues appears to shift behavior towards different options. However, it is currently not clear how alterations in cue-evoked DA release, following cocaine sensitization, impacts the effects of cue presence or absence on choice preference. The second objective of the proposed experiments will therefore be to determine how cocaine induced sensitization impacts the effects of reward-associated cues on choice preference, in delay and effort discounting task. Fast-scan cyclic voltammetry will again be used to determine associated changes in dopamine levels within the brain, during cue presentation and choice preference. Impairments in cost-benefit decision making may contribute to addiction by driving behavior towards immediate rewards requiring less effort, such as those associated with drug use (euphoria, relief from withdrawal symptoms), over more effortful, but ultimately more beneficial, rewards associated with abstinence (e.g. - better health, employment, family relationships). Understanding the role of cues, as well as the role of dopamine, in responding for rewards, particularly when different reward-cost options are available, is important to our understanding of how drugs of abuse modify behavior and decision making, as well as for the development of treatment strategies.

描述（由申请人提供）：与奖励相关的环境线索可能会影响涉及奖励响应的行动和决策。环境线索对行为选择的影响与成瘾特别相关，在成瘾中，我们看到行为控制的丧失，以及习惯性药物寻求行为的增加。奖励相关线索的呈现会刺激丘脑核（NA）内多巴胺（DA）的释放，这种效应被认为是奖励寻求增加的基础。激励敏感理论 成瘾理论认为，反复的精神兴奋剂暴露会使这个系统敏感，使刺激更容易激活DA系统并增强动机。因此，药物暴露应该允许线索与奖励配对，以施加更大的控制行为，解释成瘾个体的线索诱导的药物寻求行为的敏感性。拟议的实验的第一个目标将是确定，在大鼠中，如果可卡因敏化增强提示诱发的奖励反应和DA释放的NA，并将为我提供快速扫描循环伏安法和巴甫洛夫仪器范式的培训。将成本与大奖励选项相关联可以降低其价值，并将选择转向较小，成本较低的奖励，并且成瘾个体多次被证明比健康对照组更有可能贴现较大，更昂贵的奖励。有趣的是，奖励相关线索的存在或缺失似乎会使行为转向不同的选择。然而，目前尚不清楚如何改变线索诱发的DA释放，可卡因致敏后，影响线索的存在或不存在对选择偏好的影响。因此，所提出的实验的第二个目标将是确定可卡因诱导的敏感性如何影响奖励相关线索对选择偏好的影响，在延迟和努力折扣任务。快速扫描循环伏安法将再次用于确定在提示呈现和选择偏好期间大脑内多巴胺水平的相关变化。成本效益决策的障碍可能会导致成瘾，因为它会驱使行为倾向于需要更少努力的即时奖励，例如与药物使用相关的奖励（欣快症，戒断症状的缓解），而不是与禁欲相关的更努力，但最终更有益的奖励（例如-更好的健康，就业，家庭关系）。了解线索的作用，以及多巴胺的作用，在响应奖励，特别是当不同的奖励-成本选项是可用的，是很重要的，我们了解药物滥用如何改变行为和决策，以及治疗策略的发展。