Antidepressant-like activity of the melatonin receptor antagonist, luzindole (N-0774), in the mouse behavioral despair test.
The anti-immobility effect of the selective melatonin receptor antagonist, luzindole, was investigated in the behavioral despair test using three different strains (C3H/HeN, C57BL/6J and albino ND/4) of mice. The time of immobility of the C3H/HeN during the 240 s swimming period measured at noon (12:00 to 14:00 h) was 47.8 +/- 3.0 s (n = 63) and at midnight (00:00 to 02:00 h) was 67.7 +/- 2.8 s (n = 68) (P less than 0.001, when compared with the noon value), when the levels of endogenous melatonin are presumably low and high, respectively. Melatonin (30 mg/kg) given i.p. did not modify the time of immobility at either time of measurement. Luzindole (30 mg/kg i.p.) reduced the time of immobility in a dose-dependent manner, the effect being more pronounced at midnight (60% reduction) than at noon (39% reduction). The effect of luzindole was time-dependent, showing a maximal effect at 60 min. The anti-immobility effect of luzindole (10 mg/kg i.p.) was prevented by the administration of melatonin (30 mg/kg i.p.). Luzindole (30 mg/kg i.p.) did not modify the time of immobility either at noon or midnight in the albino ND/4 mouse, or in the C57BL/6J mouse, which does not produce melatonin. Our results suggest that endogenous melatonin plays a role during swimming in the C3H/HeN mouse behavioral despair test. We conclude that luzindole may exert antidepressant-like activity in the C3H/HeN mouse by antagonizing the action of endogenous hormone.
Dubocovich
M L
ML
Department of Pharmacology, Northwestern University Medical School, Chicago, IL 60611.
Mogilnicka
E
E
Areso
P M
PM
D000818:Animals; D000928:Antidepressive Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D002118:Calcium / Q000502:physiology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003891:Desipramine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D008550:Melatonin / Q000494:pharmacology / Q000502:physiology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism; D044094:Receptors, Melatonin; D017981:Receptors, Neurotransmitter / Q000187:drug effects; D014363:Tryptamines / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D000928:Antidepressive Agents; D044094:Receptors, Melatonin; D017981:Receptors, Neurotransmitter; D014363:Tryptamines; C057154:luzindole; D008550:Melatonin; D002118:Calcium; D003891:Desipramine; D009638:Norepinephrine