Abstract
Activation of MT1 receptors by melatonin accelerates the re‐entrainment of circadian rhythms of wheel running activity after an abrupt advance of the dark cycle (Dubocovich et al., 2005). Here, we investigated the effects of luzindole (LUZ), a competitive melatonin receptor antagonist (MT2)/inverse agonist (MT1) on the re‐entrainment rate of wheel running activity and spontaneous homecage behaviors after a 6hr advance of the dark onset in C3H/HeN mice. LUZ (10mg/kg, s.c.) given for three consecutive days at the new dark onset (8.4±0.4d, n=14) significantly increased the number of days (delay) necessary for re‐entrainment of wheel running activity rhythms compared to vehicle (VEH) controls (6.3±0.3d, n=24; p<0.001). LUZ also delays re‐entrainment of 16 spontaneous homecage behaviors recorded with the HomeCageScan System. The 16 behaviors were grouped into activity, exploratory/anxiety, ingestive and sleep behaviors. LUZ (n=8) compared to VEH (n=8) delayed re‐entrainment to dark onset of the spontaneous behaviors including activity (Walk: VEH, 9.3±o.5d & LUZ, 12.3±0.7d, p<0.005), exploratory/anxiety (Groom: VEH, 9.1±0.6d & LUZ, 12.3±0.6d, p<0.005) and ingestive (Eat: VEH, 9.5±0.5d & LUZ, 12.4±0.6d, p<0.005). We concluded that LUZ acting as inverse agonist at MT1 melatonin receptors may delay the reentrainment of wheel running and homecage behaviors. Support by NS 061068.
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