Effects of melatonin agonists and antagonists on reproduction and body weight in the Siberian hamster.
This study examined whether melatonin-induced inhibition of testicular weight and body weight in vivo could be antagonized by luzindole, a competitive melatonin receptor antagonist, or methysergide, a competitive serotonin receptor antagonist. Adult male Siberian hamsters were exposed to a long photoperiod (16L:8D) and given daily injections of drugs 3 h before lights off for 7 weeks. Hamsters treated with melatonin (0.375 mg/kg) exhibited testicular regression and loss of body weight. These effects were also marked in hamsters treated concomitantly with melatonin (0.375 mg/kg) and luzindole (10 mg/kg). In other studies, chronic injections of luzindole (30 mg/kg) to juvenile hamster failed to antagonize testicular regression induced by either melatonin injections or exposure to a short day photoperiod (12L: 12D). In contrast, concommitant injections of methysergide (6.25 mg/kg) and melatonin attenuated testicular regression and loss of body weight. When administered alone, neither luzindole nor methysergide affected testicular weight or body weight, whereas chronic injections of 5-methyoxyluzindole (10 mg/kg) mimicked the inhibitory effects of melatonin. 5-Methoxyluzindole inhibits 2-[125I]-iodomelatonin binding to median eminence/pars tuberalis membranes with an affinity similar to that of melatonin. Luzindole shows lower affinity for the inhibition of 2-[125I]-iodomelatonin binding than melatonin, which may explain why luzindole is not an effective melatonin receptor antagonist when administered in vivo. Methysergide, which has a very low affinity for inhibition of 2-[125I]-iodomelatonin binding, probably inhibits the effects of melatonin by blocking serotonergic neurotransmission.
Duncan
M J
MJ
Dept. of Anatomy and Neurobiology, University of Missouri Medical School, Columbia 65212.
Fang
J M
JM
Dubocovich
M L
ML
D000818:Animals; D001667:Binding, Competitive; D001835:Body Weight / Q000187:drug effects*; D006224:Cricetinae; D008027:Light; D008297:Male; D008473:Median Eminence / Q000378:metabolism; D008550:Melatonin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D008784:Methysergide / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects; D010507:Periodicity; D010903:Pituitary Gland, Anterior / Q000378:metabolism; D044094:Receptors, Melatonin; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors / Q000187:drug effects; D013737:Testis / Q000187:drug effects*; D014363:Tryptamines / Q000494:pharmacology
D044094:Receptors, Melatonin; D017981:Receptors, Neurotransmitter; D014363:Tryptamines; C057154:luzindole; C069247:5-methoxyluzindole; D008550:Melatonin; D008784:Methysergide