Rapid dopamine release in nucleus accumbens in Pavlovian-to-Instrumental Transfer

巴甫洛夫到仪器转移中伏隔核中多巴胺的快速释放

• 批准号: 8054829
• 负责人: Michael Saddoris
• 金额: $ 5.13万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-01 至 2013-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8054829
• 关键词: Abstinence; Address; Amphetamines; Animals; Behavior; Behavioral; Cells; Chemosensitization; Chronic; Cocaine; Complex; Consumption; Cues; Data; Dopamine; Dopamine Receptor; Drug Addiction; Electrophysiology (science); Emotions; Environment; Event; Exhibits; Food; Foundations; Goals; Health; Human; Impairment; Individual; Learning; Lesion; Location; Measurement; Measures; Mediating; Modeling; Motivation; Motor; Neurobiology; Neurons; Nucleus Accumbens; Operant Conditioning; Outcome; Output; Partner in relationship; Pharmaceutical Preparations; Pharmacological Treatment; Process; Quinine; Rattus; Relapse; Rewards; Role; Scanning; Signal Transduction; Social Environment; Stimulus; Sucrose; Techniques; Time; Water; Work; base; classical conditioning; dopaminergic neuron; drug addict; drug of abuse; insight; motivated behavior; novel; receptor; reinforcer; relating to nervous system; response; reward processing

DESCRIPTION (provided by applicant): Animals are required to seek out rewarding stimuli in their environment such as food and mates, and as such, must perform actions that will help them obtain those rewards. In addition, cues associated with desired outcomes can also motivate goal-seeking behavior. While cues associated with "natural" rewards like food may invigorate actions that will produce those outcomes, this can become pathologial in the drug addicted state, leading to relapse in drug taking even after a period of abstinence. Thus, Pavlovian cues can be powerful motivators of goal-seeking instrumental behavior. Employing a task called Pavlovian-to- lnstrumental Transfer (PIT), we can investigate this motivated behavior in normal rats and use it as a model for understanding this behavior in the addicted state. In this task, it has been demonstrated that outcome- associated cues reliably potentiate learned instrumental responses compared to baseline conditions where the cues are absent. This task has been shown to require the integrity of the nucleus accumbens (NAc), and specifically, the action of intra-accumbal dopamine (DA) to mediate this effect. However, it is currently unknown how rapid DA release events mediate the PIT effect. Using a technique known as fast scan cyclic voltammetry (FSCV), we propose to measure subsecond DA release in NAc, and compare such activity in the NAc core and shell subregions. Further, to understand how DA may influence neural encoding of discrete events in PIT, we will then employ a combined FSCV and electrophysiology technique that will allow measurement of simultaneous DA release and neural firing at the same location. In describing the relationship between DA release and NAc encoding of reward during PIT, we hope to develop the foundation for understanding the neurocircuitry involved in complex associative reward processes. This will provide a basis for understanding the neural basis of motivated behavior in both the naive and drug- addicted state. PUBLIC HEALTH: Drug addiction exacts a heavy burden on individuals and their social environments. Many addicted people are able to stop drug consumption for long periods only to relapse some time later. These bouts are often triggered by salient drug-associated cues. Understanding both the behavioral and neurobiological basis of how these cues come to take control of learned behaviors is thus of utmost importance in developing pharmacological treatments in humans.

描述（由申请人提供）：动物需要在其环境中寻找奖励刺激，例如食物和伴侣，因此必须采取行动来帮助它们获得这些奖励。此外，与期望结果相关的线索也可以激发寻求目标的行为。虽然与食物等“自然”奖励相关的线索可能会激发产生这些结果的行动，但这在吸毒成瘾状态下可能会变得病态，导致即使在戒毒一段时间后也会再次吸毒。因此，巴甫洛夫线索可以成为寻求目标的工具性行为的强大动力。采用称为巴甫洛夫仪器转移（PIT）的任务，我们可以研究正常大鼠的这种动机行为，并将其用作理解成瘾状态下这种行为的模型。在这项任务中，已经证明，与缺乏线索的基线条件相比，与结果相关的线索可靠地增强了习得的工具反应。这项任务已被证明需要伏隔核 (NAc) 的完整性，特别是伏隔内多巴胺 (DA) 的作用来介导这种作用。然而，目前尚不清楚 DA 释放事件如何介导 PIT 效应。我们建议使用快速扫描循环伏安法 (FSCV) 技术来测量 NAc 中亚秒级 DA 的释放，并比较 NAc 核和壳分区中的此类活性。此外，为了了解 DA 如何影响 PIT 中离散事件的神经编码，我们将采用 FSCV 和电生理学相结合的技术，该技术将允许在同一位置同时测量 DA 释放和神经放电。在描述 PIT 期间 DA 释放和 NAc 奖励编码之间的关系时，我们希望为理解复杂关联奖励过程中涉及的神经回路奠定基础。这将为理解幼稚状态和吸毒成瘾状态下动机行为的神经基础提供基础。 公共卫生：吸毒成瘾给个人及其社会环境带来沉重负担。许多成瘾者能够长时间戒毒，但一段时间后又复发。这些发作通常是由与药物相关的显着线索引发的。因此，了解这些线索如何控制习得行为的行为和神经生物学基础对于开发人类药物治疗至关重要。