Effects of Melatonin Agonists and Antagonists on Reproduction and Body Weight in the Siberian Hamster

Marilyn J. Duncan, Jun‐Ming ‐M Fang, Margarita L. Dubocovich

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


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 concommitantly 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.

Original languageEnglish
Pages (from-to)231-242
Number of pages12
JournalJournal of Pineal Research
Issue number4
StatePublished - Dec 1990


  • luzindole
  • methoxyluzindole
  • methysergide
  • photoperiod
  • pineal

ASJC Scopus subject areas

  • Endocrinology


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