NOCICEPTIN RECEPTORS IN REWARD CIRCUITS AND BEHAVIOR

翻译后摘要：阿片受体已成为治疗疼痛和相关条件的数千人的目标 年.三种阿片受体已被鉴定，第四种阿片受体称为伤害感受素 NOPR或阿片样受体样-1是该家族的最新成员。最近的证据表明， 阿片受体是成瘾、焦虑和抑郁的潜在新靶点。此外，报告 表明NOPR -痛敏素系统参与可卡因奖赏行为。然而，在 脑NOPR受体调节这些行为，NOPR是如何调节的，以及它是如何发出信号的， 定义了为了更好地理解这个系统在行为中的作用，我们提出了两个目标：1）我们将 确定NOPR和NOPR信号突变体在特定细胞和多巴胺能神经回路中的功能 使用靶向病毒拯救策略和行为模型来控制可卡因偏好行为。这里我们 将在小鼠中采用病毒介导的细胞类型特异性“敲入”功能获得实验，使用野生型 和突变受体来确定NOPR受体如何在多巴胺能回路中发挥作用以控制可卡因 体内偏好。2)在aim 2中，我们将使用小鼠遗传学，解剖学技术和 tDtomato-报告小鼠，以及光遗传学方法来剖析含有伤害感受素的神经元对神经元的作用。 可卡因的位置偏好，奖励和厌恶行为。这个项目和实验 这一发现为了解痛敏素-NOPR系统在药物中的作用提供了新的重要信息 虐待行为。

Abstract: Opioid receptors have been targeted for the treatment of pain and related conditions for thousands of years. Three opioid receptors have been characterized, with a fourth opioid receptor called nociceptin (NOPR) or opioid-receptor like-1 being the newest member of the family. Recent evidence has shown that opioid receptors are potentially novel targets for addiction, anxiety, and depression. Furthermore, reports suggest that the NOPR - nociceptin system is involved in cocaine reward behavior. However, where in the brain NOPR receptors modulate these behaviors, how NOPR is regulated, and how it signals has not been defined. In order to better understand the role of this system in behavior we propose 2 aims: 1) We will determine how NOPR and NOPR -signaling mutants function in specific cells and dopaminergic neural circuits to control cocaine preference behavior using targeted viral rescue strategies, and behavioral models. Here we will employ viral-mediated cell type specific "knock-in" gain-of-function experiments in mice, using wild-type and mutant receptors to determine how NOPR receptors function in dopaminergergic circuits to control cocaine preference in vivo. 2) In aim 2 we will use a combination of mouse genetics, anatomical techniques with tDtomato-reporter mice, and optogenetic approaches to dissect the role of nociceptin containing neurons on cocaine place preference, reward, and aversion behavior. Together, this project and the experiments described could provide novel and important information about nociceptin-NOPR system function in drug abuse behaviors.