Food and light as circadian time cues: characterizing motivation behavior in mice under time-restricted feeding and chronic jet lag

ACOSTA J.; CRESPO M.; PLANO S.A.; CHIESA J.J.; GOLOMBEK DA; AGOSTINO P.V.

San Diego, California

Simposio; 13th Annual Center for Circadian Biology Symposium; 2023

Most living organisms have a circadian timing system adapted to optimize the daily rhythm of exposure to the environment. This circadian system modulates several behavioral and physiological processes, including the response to natural and drug rewards. The main synchronizer agent of the circadian clock is the light-dark (LD) cycle. Changes in LD exposure can cause circadian disruption producing cognitive deficits. On the other hand, food can also act as a potent synchronizer when is temporally restricted. Under these conditions, animals display an anticipatory food activity (FAA) controlled by a food-entrainable oscillator (FEO). We have shown that motivation for food reward is regulated in a circadian manner in mice, with higher levels at night (active phase) [1]. In this work, we aim to continue characterizing the circadian modulation of motivation behavior in mice through two different approaches: when food is the main synchronizer (by time restricted feeding protocol, TRF) and when chronic phase advances in the LD cycle cause circadian disruption (by chronic jet lag protocol, CJL). In both experiments we assayed motivation through the Progressive Ratio (PR) schedule, in which subjects must increase the number of responses to earn subsequent food rewards. In the first experiment, we subjected two different groups of C57BL/6 male mice to a TRF protocol in which food was only available for 3 hours in the light (n=16) or dark (n=16) phase of the 12:12 LD cycle. Then, motivation behavior was assayed in each group at two different time points: during FAA – i.e., two hours before food availability – (n=8) and in the opposite phase to which the TRF was carried out (n=8). Our results showed that mice are highly motivated to work for food reward when FAA is present regardless of the time of day. More importantly, when FAA occurred during daytime mice presented high levels of motivation comparable to those observed at nighttime, opening the question of whether components related to reward pathways could be being synchronized to both light and food at the same time. In the second experiment, we submitted mice to a CJL protocol, which consisted of 6-hour phase advances of the LD schedule every 2 days. Then, we assayed motivation in the dark phase of CJL (n=12) and in the control group (12:12 LD, n=8). Our results showed that motivation in the CJL group was diminished compared to controls, suggesting that forced circadian desynchronization affects reward-related behaviors. Together, these findings contribute to gaining knowledge in potential mechanisms of circadian modulation of motivational states in order to improve treatment related to psychiatric disorders or drugs of abuse.References[1] Acosta, J., Bussi, I. L., Esquivel, M., Höcht, C., Golombek, D. A., & Agostino, P. V. (2020). Circadian modulation of motivation in mice. Behavioural Brain Research, 382, 112471.