Oxytocin projections mediate social and drug reward

项目摘要 物质使用障碍（SUD）在美国很普遍，超过10%的成年人符合诊断标准。 不幸的是，SUD治疗通常不成功，高达75%的患者会复发。sud是 与有问题的奖励处理有关，导致以牺牲自然奖励为代价的药物使用， 尽管有负面后果。成瘾恢复计划往往需要戒毒，同时加强 自然奖励，如社会化。研究表明，催产素的管理， 帮助这一过程并改善SUD的治疗结果。尽管催产素的治疗潜力 已经在临床试验中得到了令人鼓舞的结果，催产素对奖励的影响- 相关的神经回路还不清楚。 大多数研究指出，催产素降低了药物的强化作用，但增加了社会的显着性， 刺激。奖赏刺激的检测部分由中脑边缘多巴胺系统调节， 腹侧被盖区（VTA）中投射至丘脑核（NAc）的多巴胺能细胞体。 新出现的证据表明，不同的回路促进药物与社会奖励，药物奖励 取决于阶段性（快速爆发）多巴胺释放和对紧张性（缓慢，稳定）多巴胺的社会奖励 在NAC中释放。催产素对成瘾的治疗效果可能是催产素转移多巴胺的结果 从阶段性到紧张性的释放模式，从而重新平衡促进药物和社会奖励的途径。的 目前的建议将评估催产素的预测和催产素受体位于奖励相关的作用， 大脑区域对药物与社会奖励的偏好以及阶段性与紧张性多巴胺释放的偏好。 这项拟议的研究将是第一个系统地调查神经通路和受体网站利用 催产素来调节奖赏加工。拟议的研究采用了当代技术， 操纵神经回路（DREADD和CRISPR/Cas9技术）和创造性的扭曲条件 位置偏好测试和体内多巴胺定量。阐明催产素 介导药物和社会奖励对于充分利用催产素治疗SUD的潜力至关重要。

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. 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 current proposal will assess the role of oxytocin projections and oxytocin receptors located in reward-related brain regions on preference for drug vs social reward and phasic vs tonic dopamine release. The proposed study will be the first to systematically investigate the neural pathways and receptor sites utilized by oxytocin to mediate reward processing. The proposed study incorporates contemporary techniques for manipulating neural circuits (DREADD and CRISPR/Cas9 technologies) and inventive twists on conditioned place preference testing and in vivo dopamine quantification. Clarifying the mechanisms by which oxytocin mediates drug and social reward is crucial for harnessing the full therapeutical potential of oxytocin for SUD.