小柯机器人

近日，美国西奈山伊坎医学院Eric J. Nestler等研究人员合作发现，滥用药物可劫持处理稳态需求的一条中脑边缘通路。该研究于2024年4月19日发表于国际一流学术期刊《科学》。

利用全脑FOS图谱和体内单神经元钙成像技术，研究人员发现滥用药物会增强伏隔核（NAc）中多巴胺感受器的集合活动，并以细胞类型特异性的方式扰乱对自然奖赏的重叠集合反应。结合FOS-Seq、CRISPR扰动和单核RNA测序，研究人员发现Rheb是一种分子底物，它能调节NAc中细胞类型特异性信号转导，同时使药物抑制自然奖赏消耗。

绘制滥用药物激活的NAc投射区域图，揭示对自然奖赏消耗的输入特异性影响。这些发现揭示了一种常见奖赏通路的动态、分子和回路基础，在这种通路中，滥用药物会干扰先天需求的满足。

研究人员表示，滥用药物被认为部分是通过“劫持”大脑奖赏系统来促进成瘾的，但其潜在机制仍未确定。

附：英文原文

Title: Drugs of abuse hijack a mesolimbic pathway that processes homeostatic need

Author: Bowen Tan, Caleb J. Browne, Tobias Nbauer, Alipasha Vaziri, Jeffrey M. Friedman, Eric J. Nestler

Issue&Volume: 2024-04-19

Abstract: Drugs of abuse are thought to promote addiction in part by “hijacking” brain reward systems, but the underlying mechanisms remain undefined. Using whole-brain FOS mapping and in vivo single-neuron calcium imaging, we found that drugs of abuse augment dopaminoceptive ensemble activity in the nucleus accumbens (NAc) and disorganize overlapping ensemble responses to natural rewards in a cell type–specific manner. Combining FOS-Seq, CRISPR-perturbation, and single-nucleus RNA sequencing, we identified Rheb as a molecular substrate that regulates cell type–specific signal transduction in NAc while enabling drugs to suppress natural reward consumption. Mapping NAc-projecting regions activated by drugs of abuse revealed input-specific effects on natural reward consumption. These findings characterize the dynamic, molecular and circuit basis of a common reward pathway, wherein drugs of abuse interfere with the fulfillment of innate needs.

DOI: adk6742

Source: https://www.science.org/doi/10.1126/science.adk6742