pnVTA痛敏肽环路可以抑制获取奖赏的动机，这一成果由华盛顿大学医学院Michael R. Bruchas研究团队取得。 相关论文于2019年7月25日发表在国际顶尖学术期刊《细胞》上。

研究团队分析了痛敏肽环路在寻求奖赏中的作用。课题组制作了一个前痛敏肽（PNOC）CRE小鼠系，揭示了一个独特的亚群，即富含前痛敏肽的与黒质并行的腹侧被盖区（pnVTA）神经元。光纤光度测定法记录钙信号显示，当小鼠停止寻求自然奖励时，pnVTA PNOC神经元变得非常活跃。选择性pnVTA PNOC神经元切除、抑制和条件性VTA痛敏肽受体（nopr）缺失增加了操作性反射的反应，表明PNVTA PNOC核和VTA nopr信号是调节奖赏动机的必要条件。此外，这种pnVTA PNOC核团的光遗传学和化学遗传学激活导致回避行为和奖励动机降低。这些发现通过识别一种以前未知的包含神经肽的pnVTA核团对奖励动机的抑制，提供了对调节动机行为的神经调节环路的洞察。

研究人员表示，痛敏肽及其受体广泛分布于大脑中与奖赏行为相关的区域，但它们的作用方式和时间尚不清楚。

附：英文原文

Title: A Paranigral VTA Nociceptin Circuit that Constrains Motivation for Reward

Author: Kyle E. Parker, Christian E. Pedersen, Adrian M. Gomez, Joseph D. Dougherty, Garret D. Stuber, Michael R. Bruchas

Issue&Volume: 25 JULY 2019

Abstract: Nociceptin and its receptor are widely distributed throughout the brain in regions associated with reward behavior, yet how and when they act is unknown. Here, we dissected the role of a nociceptin peptide circuit in reward seeking. We generated a prepronociceptin ( Pnoc)-Cre mouse line that revealed a unique subpopulation of paranigral ventral tegmental area (pnVTA) neurons enriched in prepronociceptin. Fiber photometry recordings during progressive ratio operant behavior revealed pnVTA Pnoc neurons become most active when mice stop seeking natural rewards. Selective pnVTA Pnoc neuron ablation, inhibition, and conditional VTA nociceptin receptor (NOPR) deletion increased operant responding, revealing that the pnVTA Pnoc nucleus and VTA NOPR signaling are necessary for regulating reward motivation. Additionally, optogenetic and chemogenetic activation of this pnVTA Pnoc nucleus caused avoidance and decreased motivation for rewards. These findings provide insight into neuromodulatory circuits that regulate motivated behaviors through identification of a previously unknown neuropeptide-containing pnVTA nucleus that limits motivation for rewards.

DOI: DOI:https://doi.org/10.1016/j.cell.2019.06.034

Source: https://www.cell.com/cell/fulltext/S0092-8674(19)30737-8#