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Effects of the Melatonin Receptor Antagonist (MT2)/Inverse Agonist (MT1) Luzindole on Re‐entrainment of Wheel Running Activity and Spontaneous Homecage Behaviors in C3H/HeN Mice
Author(s) -
Adamah-Biassi Ekue Bright,
Stepien Iwona,
Hudson Randall L,
Dubocovich Margarita L
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1042.5
Subject(s) - luzindole , agonist , entrainment (biomusicology) , melatonin , medicine , endocrinology , circadian rhythm , inverse agonist , antagonist , receptor , chemistry , rhythm
Activation of MT 1 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 (MT 2 )/inverse agonist (MT 1 ) 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 MT 1 melatonin receptors may delay the reentrainment of wheel running and homecage behaviors. Support by NS 061068.