小柯机器人

2021年10月13日出版的《自然》杂志在线发表美国华盛顿大学Michael R. Bruchas、Daniel C. Castro研究团队的最新研究成果。他们揭示了内源性阿片类回路决定状态相关的奖励消费。

在本研究中，研究人员发现小鼠内源性µ-阿片肽受体(MOPR)通过特定中缝背向伏隔核投射调节奖励消费。MOPR介导的中缝末端抑制对于确定完成反应是必要且足够的，而选择含脑啡肽的伏隔核集合在奖励消耗之前参与，这表明局部脑啡肽释放是内源性MOPR配体的来源。伏隔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。这些结果确定了状态依赖性消费行为的基本内源性阿片类回路，并提出了阿片类药物调节奖励的替代机制。 

据了解，MOPR刺激会改变呼吸、镇痛和奖励行为，并可能导致药物滥用和过量服用。尽管其重要性显而易见，但MOPR调节完成行为的内源性机制仍然未知。

附：英文原文

Title: An endogenous opioid circuit determines state-dependent reward consumption

Author: Castro, Daniel C., Oswell, Corinna S., Zhang, Eric T., Pedersen, Christian E., Piantadosi, Sean C., Rossi, Mark A., Hunker, Avery C., Guglin, Anthony, Morn, Jose A., Zweifel, Larry S., Stuber, Garret D., Bruchas, Michael R.

Issue&Volume: 2021-10-13

Abstract: μ-Opioid peptide receptor (MOPR) stimulation alters respiration, analgesia and reward behaviour, and can induce substance abuse and overdose1,2,3. 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.

DOI: 10.1038/s41586-021-04013-0

Source: https://www.nature.com/articles/s41586-021-04013-0

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
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