图1所示。酒精诱导的边缘下mGluR2缺陷导致自体免疫试验性能受损。(A)长期酒精蒸汽暴露方案导致血液酒精浓度稳定,并显著增加躯体戒断评分。禁欲3周后,分批动物被用于脊柱密度分析、注意力转移测试(自体试验)或慢病毒边缘下mGluR2抢救。(B)自体试验计划,大鼠必须根据嗅觉或触觉线索/尺寸作出一系列的鉴别选择。与对照大鼠(n = 15,白圈)相比,酒精依赖[后依赖(PD), n = 14,黑色方块]大鼠在IDS和EDS子任务中需要明显更多的试验来判定。(C)延迟折扣任务(DDT)方案。下图代表了对高奖励的偏好与高奖励在时间上的延迟的百分比。与对照组相比,酒精依赖大鼠具有更陡峭的曲线(均值±SEM)。(D) P大鼠过早终止密码子基因组位置示意图(50)。(E) Alcohol-naïve印第安纳P大鼠(n = 12,黑色三角形)与印第安纳NP大鼠(n = 12,白色三角形)相比,在IDS/EDS任务中没有差异。 (F) Schematic representation of lentiviral constructs. Lenti-mGluR2 expresses Grm2 and cop green fluorescent protein (copGFP) under control of elongation factor 1-alpha (EF1α) promoter. Lenti-control only expresses copGFP under EF1α control. ENV; Epstein-Barr virus derived vector, cPPT; central polypurine tract, WPRE; Woodchuck posttranscriptional regulatory element. (G) Injection placements are represented by black circles. Injection sites were verified within the infralimbic cortex from +3.2 to +2.2 mm anterior to bregma (85). (H) ASST performance of PD rats injected with either lenti-mGluR2 (n = 16, red squares) or lenti-control (n = 16, black squares) into the infralimbic cortex. In the EDS component of the task, no difference was observed between control and virally infected PD rats. However, in the IDS component, lenti-mGluR2–injected animals overall needed significantly fewer trials to criterion. IDS, intradimensional shift; EDS, extradimensional shift; *P < 0.05, **P < 0.01, and ***P < 0.001. Credit: DOI: 10.1126/sciadv.abh2399