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: 8235039
• 负责人: Michael Saddoris
• 金额: $ 5.39万
• 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/8235039
• 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; 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）：需要动物在食物和伴侣等环境中寻找奖励刺激，因此必须采取行动，以帮助他们获得这些奖励。此外，与期望结果相关的提示也可以激发寻求目标的行为。尽管与食物这样的“自然”奖励相关的提示可能会激发产生这些结果的行动，但在毒品上瘾状态下这可能会变得病理性，即使在禁欲后，药物服用也会复发。因此，帕夫洛夫提示可能是寻求目标工具行为的有力动力。采用一个称为帕夫洛夫到劳动转移（PIT）的任务，我们可以调查正常大鼠中的这种动机行为，并将其用作在上瘾状态中理解这种行为的模型。在这项任务中，与缺乏线索的基线条件相比，与结果相比，结果相关的线索可靠地增强了学术的工具反应。该任务已被证明需要伏隔核（NAC）的完整性，具体来说， - 辅助多巴胺（DA）的作用以介导这种效果。但是，目前尚不清楚DA释放事件如何介导PIT效应。使用称为快速扫描循环伏安法（FSCV）的技术，我们提议测量NAC中的二释放释放，并比较NAC核心和壳子区域中的这种活性。此外，为了了解DA如何影响PIT中离散事件的神经编码，我们将采用合并的FSCV和电生理技术，该技术将允许在同一位置测量同时释放DA和神经射击。在描述DA释放与NAC编码奖励期间的关系时，我们希望为理解复杂的关联奖励过程中涉及的神经循环发展奠定基础。这将为理解天真和毒品上瘾状态的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的负担。许多上瘾的人能够长时间停止吸毒，只有一段时间以后就可以复发。这些回合通常是由显着的药物相关线索触发的。因此，了解这些暗示如何控制学到的行为的行为和神经生物学基础对于开发人类的药理学治疗至关重要。