Felix P Mayer, Hideki Iwamoto, Maureen K Hahn, Gregory J Grumbar, Adele Stewart, Yulong Li, Randy D Blakely
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.
