Peripheral Inflammation and Sleep Loss Induce Coordinated Motivational Changes: An Experimental Two-Hit Stress Model.

Sleep loss and low-grade inflammation are common stressors that affect behaviour and recovery needs. To examine their separate and combined effects on motivation for everyday behaviours, we developed a two-hit experimental model. Participants (N = 56, 31 women) completed three experimental visits: sleep saturation (two nights, 9 h in bed/night); sleep-restriction (two nights, 4 h in bed/night); and an immune challenge (~24 h post COVID-19 vaccination) combined with either sleep saturation (n = 26) or restriction (n = 30). Motivation for everyday behaviours and sleepiness were rated, and blood samples were collected. Both sleep restriction and vaccination increased motivation for sleep-related behaviours and reduced motivation for physical and social activity, with sleep restriction having broader effects. These changes were associated with inflammation and sleepiness. Vaccination increased thirst, while sleep restriction reduced it, but neither affected hunger or food preferences. Sleep restriction amplified the inflammatory response to vaccination. For motivation, the stressors combined caused larger changes than either alone for some outcomes, without amplifying one another. These findings support that different stressors reallocate motivation towards rest and sleep-supporting behaviours over physical and social activity, likely to drive behaviours that support homeostasis after allostatic challenges. As these stressors often co-occur, this adaptive response can meaningfully shape daily functioning. Future work may determine when this functional response becomes maladaptive.