Acute Restraint Stress Alters Wheel-running Behavior Immediately Following

27 In vertebrates, acute stressors, although short in duration, can influence physiology and behavior 28 over a longer time course, which might have important ramifications under natural conditions. In 29 laboratory rats, for example, acute stress has been shown to increase anxiogenic behaviors for days 30 after a stressor. In the present study, we quantified voluntary wheel-running behavior for 22 hours 31 following a restraint stress, and glucocorticoid levels 24 hours post-restraint. We utilized mice 32 from four replicate lines that have been selectively bred for high voluntary wheel-running activity 33 (HR mice) for 60 generations and their non-selected Control (C) lines, to examine potential 34 interactions between exercise propensity and sensitivity to stress. Following six days of wheel 35 access on a 07:00-19:00 photocycle (as during the routine selective-breeding protocol), 80 mice 36 were physically restrained for 40 minutes, beginning at 14:00, while another 80 were left 37 undisturbed. Relative to unrestrained mice, wheel running increased for both HR and C mice 38 during the first hour post-restraint (P < 0.0001), but did not differ two or three hours post-restraint. 39 Wheel running was also examined at four distinct phases of the photoperiod. Running in the 40 period 16:00-18:40 was unaffected by restraint stress and did not differ statistically between HR 41 and C mice. During the period of peak wheel running (19:20-01:40), restrained mice tended to run 42 fewer revolutions (-11%: 2-tailed P = 0.0733), while HR mice ran 473% more than C (P = 43 0.0008), with no restraint-by-linetype interaction. As wheel running declined in the latter part of 44 the scotophase (01:40-06:00), restraint still had no statistical effect on wheel running, but HR 45 again ran more than C (+467%: P = 0.0122). Finally, during the start of the photophase (07:20-46 12:00), restraint increased running by an average of 53% (P = 0.0443) in both linetypes, but HR 47 and C mice did not differ statistically. Mice from HR lines had statistically higher plasma 48 corticosterone concentrations than C mice, with no statistical effect of restraint and no interaction 49 between linetype and restraint. Overall, these results indicate that acute stress can affect 50 3 locomotor activity (or activity patterns) for many hours, with the most prominent effect being an 51 increase in activity during a period of typical inactivity at the start of the photophase, 15-20 hours 52 post-stressor. 53 vigilance, voluntary exercise. 55 56 …