Oxytocin Mediates Phasic and Tonic Dopamine Release

催产素介导阶段性和强直性多巴胺释放

• 批准号: 10575856
• 负责人: Deranda B Lester
• 金额: $ 6.94万
• 依托单位: UNIVERSITY OF MEMPHIS
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-15 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10575856
• 关键词: Adult; Affect; Agonist; Anesthesia procedures; Attenuated; Autoreceptors; Brain region; Cell Nucleus; Cells; Clinical; Clinical Trials; Complex; Detection; Diagnosis; Dopamine; Dopamine D2 Receptor; Dopaminergic Cell; Dose; Drug usage; Electrodes; FDA approved; Female; Fire - disasters; Future; Gender; Infusion procedures; Location; Mediating; Mus; Neuropeptides; Nucleus Accumbens; Outcome; Oxytocin; Oxytocin Receptor; Pathway interactions; Patients; Pattern; Periodicity; Peripheral; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Process; Receptor Activation; Recovery; Relapse; Research; Rewards; Scanning; Site; Social Behavior; Socialization; Stimulus; Structure; Substance Use Disorder; System; Techniques; Therapeutic; Therapeutic Effect; Treatment outcome; Ventral Tegmental Area; addiction; behavioral response; biological adaptation to stress; dopaminergic neuron; drug abstinence; drug reward; experience; improved; in vivo; male; meetings; mesolimbic system; neural; neural circuit; neurochemistry; novel; programs; psychostimulant; response; reward processing; sex; social; stimulant use disorder; substance use treatment

Project Summary Substance use disorder (SUD) is prevalent in the US with over 10% of adults fitting the criteria for diagnosis. Unfortunately, SUD treatments are often unsuccessful, with up to 75% of patients experiencing relapse. SUD is associated with problematic reward processing, leading to drug use at the expense of natural rewards and despite negative consequences. Addiction recovery programs often require drug abstinence while reinforcing engagement with natural rewards such as socialization. Research suggests that oxytocin administration could help with this process and improve treatment outcomes for SUD. Although the therapeutic potential of oxytocin is already being investigated in clinical trials with encouraging outcomes, the effects of oxytocin on reward- related neural circuits are not understood. The current proposal will assess the region-specific influence of oxytocin receptor activation on neurochemical release associated with drug and social reward processing. Most studies point to oxytocin decreasing the reinforcing effects of drugs but increasing the salience of social stimuli. The detection of rewarding stimuli is regulated in part by the mesolimbic dopamine system, with dopaminergic cell bodies in the ventral tegmental area (VTA) that project to the nucleus accumbens (NAc). Emerging evidence suggests that different circuits facilitate drug versus social reward, with drug reward depending on phasic (fast bursts) dopamine release and social reward on tonic (slow, steady) dopamine release in the NAc. Oxytocin’s therapeutic effects for addiction may be a result of oxytocin shifting dopamine release patterns from phasic to tonic, thus rebalancing the pathways facilitating drug and social reward. The proposed study will be the first to systematically investigate the neural regions in which oxytocin mediates phasic and tonic mesolimbic dopamine release. Using an established electrochemical technique (fast scan cyclic voltammetry), we will assess in vivo phasic and tonic dopamine release following microinfusions of a selective oxytocin receptor agonist into the NAc or VTA. Clarifying the mechanisms by which oxytocin mediates drug and social reward is crucial for harnessing the full therapeutical potential of oxytocin for SUD.

项目摘要 在美国，药物使用障碍（SUD）普遍存在，超过10％的成年人适合诊断标准。 不幸的是，SUD治疗通常不成功，多达75％的患者患有继电器。 SUD是 与问题的奖励处理相关，导致吸毒以牺牲自然奖励和 尽管后果负面影响。成瘾恢复计划通常需要戒毒，同时加强毒品 参与自然奖励，例如社会化。研究表明，催产毒素可以 帮助这一过程并改善SUD的治疗结果。虽然催产素的治疗潜力 已经在临床试验中进行了调查，令人鼓舞的结果，氧气对奖励的影响 - 相关的神经回路尚不清楚。 当前的建议将评估氧受体激活对神经化学的区域特异性影响 释放与毒品和社会奖励处理相关。大多数研究表明氧降低了 增强药物的影响，但增加了社会刺激的显着性。奖励刺激的检测是 部分由中唇多巴胺系统调节，腹侧段的多巴胺能细胞体 该项目（VTA）向伏隔核（NAC）投射。新兴的证据表明不同的电路 促进药物与社会奖励，并获得药物奖励，具体取决于阶段性（快速爆发）多巴胺的释放和 在NAC中释放补品（缓慢，稳定）多巴胺的社会奖励。催产素对成瘾的治疗作用 可能是氧加毒素转移多巴胺释放模式从质量到滋补的结果，因此重新平衡了 支持药物和社会奖励的途径。 拟议的研究将是第一个系统地研究氧介导的神经区域的研究 阶段性和滋补性中唇多巴胺释放。使用已建立的电化学技术（快速扫描） 循环伏安法），我们将在微吸收后评估体内阶段性和补品多巴胺释放 选择性氧毒素受体激动剂进入NAC或VTA。阐明氧加毒素的机制 介导药物和社会奖励对于利用氧气的全部治疗潜力至关重要。