Sleep-wake cycle and behavioral disturbance in a mouse model of frustrative nonreward

AbstractDaily time-restricted access to a palatable reward triggers anticipatory behavior that can synchronize an animals internal clock and adjust its behavioral rhythms. The unexpected violation of this reward expectancy can induce a negative emotion usually referred to as "frustration". Frustration responses have been characterized in rodents using a reward downshift paradigm. Although an anxiogenic effect of this reward downshift has been described, the associated long-term locomotor and behavioral patterns remain understudied. Furthermore, changes in the sleep preparatory behavior or in sleep per se associated with sudden reward downshift currently remain underexplored. In this study, we combined wireless electrocorticographic/electromyographic (ECoG/EMG) recordings, accelerometer and video recordings in freely behaving mice to determine sleep-wake, locomotor and behavioral patterns associated with a reward downshift paradigm. Our results show an initial increase in locomotor activity and increased latency to rest following reward devaluation. Furthermore, we found that downshifted mice displayed a reduced number of episodes of rapid-eye-movement sleep (REMs) during the light phase, and increased latency to non-REMs and REMs on the first two days post-shift. Additionally, we found decreased locomotor activity and reduced nest quality over the first two days post-shift compared to unshifted animals. Our results suggest that frustration induces a transient anxiogenic effect followed by a depressive-like state. Of note, our study has the strength of using a novel approach for home-cage behavior analysis that combines machine-learning-based tracking, long-term average body-acceleration, ECoG/EMG recordings, and home-cage nest quality assessment.