School of Psychology, UNSW Sydney, 2052, Australia.
The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, 3052, Australia.
Neuron. 2018 May 2;98(3):512-520.e6. doi: 10.1016/j.neuron.2018.03.033. Epub 2018 Apr 12.
Contexts exert bi-directional control over relapse to drug seeking. Contexts associated with drug self-administration promote relapse, whereas contexts associated with the absence of self-administration protect against relapse. The nucleus accumbens shell (AcbSh) is a key brain region determining these roles of context. However, the specific cell types, and projections, by which AcbSh serves these dual roles are unknown. Here, we show that contextual control over relapse and abstinence is embedded within distinct output circuits of dopamine 1 receptor (Drd1) expressing AcbSh neurons. We report anatomical and functional segregation of Drd1 AcbSh output pathways during context-induced reinstatement and extinction of alcohol seeking. The AcbSh→ventral tegmental area (VTA) pathway promotes relapse via projections to VTA Gad1 neurons. The AcbSh→lateral hypothalamus (LH) pathway promotes extinction via projections to LH Gad1 neurons. Targeting these opposing AcbSh circuit contributions may reduce propensity to relapse to, and promote abstinence from, drug use.
背景对药物寻求的复燃施加双向控制。与药物自我给药相关的背景会促进复燃，而与自我给药缺失相关的背景则会预防复燃。伏隔核壳（AcbSh）是决定这些背景作用的关键脑区。然而，尚不清楚 AcbSh 通过哪些特定的细胞类型和投射来发挥这双重作用。在这里，我们表明，对复燃和戒断的背景控制嵌入到多巴胺 1 受体（Drd1）表达的 AcbSh 神经元的不同输出回路中。我们报告了在酒精寻求引发的复燃和消退期间，Drd1 AcbSh 输出途径的解剖和功能分离。AcbSh→腹侧被盖区（VTA）途径通过投射到 VTA Gad1 神经元来促进复燃。AcbSh→外侧下丘脑（LH）途径通过投射到 LH Gad1 神经元来促进消退。靶向这些相反的 AcbSh 回路贡献可能会降低对药物使用的复燃倾向，并促进戒断。
