SEROTONIN AND FEEDBACK EFFECTS OF BEHAVIORAL ACTIVITY ON CIRCADIAN-RHYTHMS IN MICE

Wheel running activity can shorten the period (tau) of circadian rhyth ms in rats and mice. The role of serotonin (5HT), in this effect of be havior on circadian pacemaker function, was assessed by measuring tau during wheel-open and wheel-locked conditions in mice sustaining neuro toxic 5HT lesions directed at the suprachiasmatic nucleus (SCN). Intac t mice exhibited a significant lengthening of tau (similar to 10 min) within 3 weeks when running wheels were locked. Mice with immunocytoch emically confirmed 5HT depletion showed significantly longer tau than intact mice during wheel access, and did not show a significant change in tau up to 6 weeks after wheels were locked. In these mice, variabi lity of tau across wheel access conditions was similar in magnitude to tau variability in intact mice at two time points without wheel acces s (+/- 3 min). 5HT-depleted mice also exhibited significantly longer a ctivity periods (alpha), and a significantly delayed peak of activity within alpha. Previous studies show that a delayed peak of activity wi thin alpha is associated with longer tau. Group differences in tau, an d apparent failure of wheel-locking to lengthen tau in mice with 5HT l esions, may thus be due to loss of a serotonergic behavioral input pat hway to the SCN, or to a lesion-induced change in the waveform of the activity rhythm. (C) 1998 Elsevier Science B.V. All rights reserved.