Various stimuli have been employed as reinforcers in preclinical rodent models to elucidate the underpinnings of reward at a molecular and circuit level, with the release of dopamine (DA) in the nucleus accumbens (NAc) as a well-replicated, physiological correlate. Many factors, however, including strain differences, sex, prior stress, and reinforcer administration protocols can influence reward responding and DA release. Although previous evidence indicates that access to the home cage can be an effective reinforcer in behavioral tasks, whether this simple environmental manipulation can trigger DA release in the NAc has not been demonstrated. Here, using fiber photometric recordings of in vivo NAc dopamine release from a genetically-encoded DA sensor, we show that the movement of animals from the home cage to a clear, polycarbonate recording chamber evokes little to no DA release following initial exposure whereas returning animals from the recording chamber to a clean, home-like cage or to the home cage robustly triggers the release of DA, comparable in size to that observed with a 10 mg/kg i.p. Cocaine injection in the recording chamber. Although DA release can be evoked in moving mice to a clean cage, this release was significantly augmented when moving animals from the clean cage to the home cage. Our data provide direct evidence that home cage return from a foreign environment results in a biochemical change consistent with that of a rewarding stimulus. This simple environmental manipulation provides a minimally invasive approach to study the reward circuitry underlying an ethologically relevant reinforcer, return to the safe confines of “home”. The home cage – DA release paradigm may also represent a biomarker-driven paradigm for the evaluation of genetic and experiential events that underlie anhedonic states, characteristic of major mood disorders, and to present new opportunities to identify their treatments.

各种刺激已被用作临床前啮齿动物模型中的强化物，以阐明分子和电路水平上奖励的基础，伏隔核 (NAc) 中多巴胺 (DA) 的释放是一种复制良好的生理相关物。然而，许多因素，包括应变差异、性别、先前的压力和强化剂管理协议，都会影响奖励反应和 DA 释放。尽管先前的证据表明进入家庭笼子可以成为行为任务中的有效强化物，但这种简单的环境操作是否可以触发 NAc 中的 DA 释放尚未得到证实。在这里，使用体内纤维光度记录NAc 多巴胺从基因编码的 DA 传感器中释放，我们展示了动物从笼子到清晰的聚碳酸酯记录的运动腔室在初始暴露后几乎不会引起 DA 释放，而将动物从记录室返回到干净的、像家一样的笼子或家笼会强烈地触发 DA 的释放，其大小与 10 mg/kg ip 观察到的大小相当在录音室注射可卡因。虽然在将小鼠移动到干净的笼子时可以引起 DA 释放，但是当将动物从干净的笼子移动到家笼时，这种释放会显着增加。我们的数据提供了直接证据，表明从外来环境返回的笼子会导致与奖励刺激一致的生化变化。这种简单的环境操作提供了一种微创方法来研究行为相关强化物背后的奖励回路，回到“家”的安全范围。