µ-Opioid peptide receptor (MOPR) stimulation alters respiration, analgesia and reward behaviour, and can induce substance abuse and overdose^1,2,3. Despite its evident importance, the endogenous mechanisms for MOPR regulation of consummatory behaviour have remained unknown⁴. Here we report that endogenous MOPR regulation of reward consumption in mice acts through a specific dorsal raphe to nucleus accumbens projection. MOPR-mediated inhibition of raphe terminals is necessary and sufficient to determine consummatory response, while select enkephalin-containing nucleus accumbens ensembles are engaged prior to reward consumption, suggesting that local enkephalin release is the source of the endogenous MOPR ligand. Selective modulation of nucleus accumbens enkephalin neurons and CRISPR–Cas9-mediated disruption of enkephalin substantiate this finding. These results isolate a fundamental endogenous opioid circuit for state-dependent consumptive behaviour and suggest alternative mechanisms for opiate modulation of reward.

μ-阿片肽受体 (MOPR) 刺激会改变呼吸、镇痛和奖赏行为，并可能诱发药物滥用和用药过量^1,2,3 。尽管其重要性显而易见，但 MOPR 调节完成行为的内生机制仍然未知⁴ 。在这里，我们报道了小鼠奖赏消耗的内源性 MOPR 调节通过特定的中缝背侧到伏隔核投射来发挥作用。 MOPR 介导的中缝末端抑制对于确定完成反应是必要且充分的，而选择的含有脑啡肽的伏隔核群在奖赏消耗之前参与，表明局部脑啡肽释放是内源性 MOPR 配体的来源。伏核脑啡肽神经元的选择性调节和 CRISPR-Cas9 介导的脑啡肽破坏证实了这一发现。这些结果分离了状态依赖性消费行为的基本内源性阿片类药物回路，并提出了阿片类药物奖励调节的替代机制。