Development of Wireless Equipment for Autonomous Rodent Infusion Tasks

项目摘要 尽管在临床前和临床成瘾领域都取得了重大进展， 物质使用障碍（SUD）和致命的过量结果在过去不断增加 二十年为了解决这一令人担忧的健康问题，需要转化啮齿动物模型来揭示神经系统。 回路以及SUD发展和维持的细胞和分子机制。在 在这方面，静脉内自我给药程序是啮齿动物SUD模型的金标准。然而，在这方面， 尽管是最可靠的程序之一，具有明确的表面有效性，但该程序仍然受到其 拴系的性质，限制其使用的有限空间，其中啮齿动物暴露于未丰富的 食物、水或社会互动有限或无法获得的环境。设置或环境是一个关键 SUD的组成部分。在啮齿类动物模型中，证据表明，意志性社会互动和 非社会奖励，如车轮运行，和操作员提供可口的食物，可以减少 消耗，升级和恢复药物自我给药。在这里，我们建议使用我们的 在无线技术、设备开发和药物滥用责任的啮齿动物模型方面的互补专业知识 建立无线控制的静脉自我给药实验， 相关环境，如丰富的实验室家庭环境。虽然无线药物给药装置具有 以前开发的这些方法仅允许小体积和有限数量的受控输注。 静脉内自我给药程序通常由长期每日疗程组成，在此期间， 评估药物滥用责任需要多次受控药物摄入，因此需要更大的药物量。到 解决这一限制，并允许在富集的实验室家庭笼中评估药物滥用的责任， 建议1）开发一种与静脉留置导管连接的无线控制的可穿戴药物储存器 以及2）使用蓝牙网状技术来实现基于家庭护理的静脉内自我给药程序 使用交互式连接设备。我们设想，这些新的开源方法将扩大 临床前SUD模型的转化价值，使新的实验设计，以改善目前的 旨在开发药物使用障碍治疗方法的战略。

PROJECT SUMMARY Despite major advances in both the preclinical and clinical addiction fields, the number of US citizens afflicted by substance use disorders (SUDs) and the lethal overdose outcomes has continuously increased over the past two decades. To tackle this alarming health issue, translational rodent models are needed to uncover the neural circuits and the cellular and molecular mechanisms underlying the development and maintenance of SUDs. In this regard, intravenous self-administration procedures is the gold standard for rodent SUD models. However, despite being one of the most reliable procedures, with clear face validity, this procedure is still limited by its tethered nature, constraining its use to restricted spaces in which rodents are exposed to unenriched environments with limited or no access food, water, or social interaction. The setting or environment is a critical component of SUD. In rodent models, evidence has shown that availability for volitional social interaction and non-social rewards such as wheel running, and operant-delivered palatable foods can decrease the consumption, the escalation, and the reinstatement in drug self-administration. Here we propose to use our complementary expertise in wireless technology, device development, and rodent models of drug abuse liability to establish wirelessly controlled intravenous self-administration experiments in complex and more ethologically- relevant environments such as enriched laboratory homecages. While wireless drug administration devices have previously been developed, they only allow for small volume and restricted number of controlled infusions. Intravenous self-administration procedures are generally composed of long-term daily session during which multiple controlled drug intakes and thus larger drug volumes are necessary to assess drug abuse liability. To tackle this limitation and permit the assessment of drug abuse liability in enriched laboratory home cages we propose to 1) develop a wireless-controlled wearable drug reservoir connected to intravenous indwelling catheter and 2) use Bluetooth mesh technology to enable homecage-based intravenous self-administration procedures using interactive connected devices. We envision that these new open-source approaches will broaden the translational value of pre-clinical SUD models by enabling new experimental designs to improve current strategies aiming at developing substance use disorders treatments.