Acute low doses of melatonin stimulate rat sex behavior: the role of serotonin neurotransmission

Eur J Pharmacol. 1999 Nov 26;385(1):1-6. doi: 10.1016/s0014-2999(99)00701-3.


Melatonin is known to inhibit male and female sex behavior, but this effect has been reported only after repeated administration of sustained doses of the hormone. The present experiments were performed in order to study the effects of acute treatment with low doses of melatonin on rat male and female sex behavior in a dose-response paradigm. After four mating tests with a receptive female, sexually active male rats of the Wistar strain were injected intraperitoneally (i.p.) with small doses of melatonin (10, 50 and 100 microg/kg) administered acutely 1 h before a 30-min mating test. Melatonin (50 and 100 ng/2 microl) or its analogs, 6-chloromelatonin (2 and 4 ng/2 microl) and 2-iodomelatonin (5 and 10 ng/2 microl) were also injected intracerebroventricularly (i.c.v.) 30 min before mating. Either treatments caused a reduction of the latency to the first mount, intromission and ejaculation. An increase in the frequency of mounts, intromissions and ejaculations was also observed. Inhibition of sexual activity was observed when a greater dose (1 mg/kg) of melatonin was repeatedly injected for 14 days. Female sex behavior, measured by the lordosis quotient in Wistar female rats, was not affected by acute treatment with the hormone, while it appeared to be inhibited by the repeated injection. The facilitating effect of acute i.p. or i.c.v. melatonin low doses on sexual activity of male rats was partially abolished by the pre-treatment with the non-selective melatonin antagonist, luzindole (0.25 mg/kg, injected subcutaneously), and totally suppressed by the injection of small quantities of serotonin or the 5H(2A)-5H(2C) receptor agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane into the amygdala. These results suggest that melatonin may exert opposite effects on male and female sex behavior depending on the dose and duration of treatment.

MeSH terms

  • Amphetamines / pharmacology
  • Animals
  • Dose-Response Relationship, Drug
  • Ejaculation / drug effects
  • Female
  • Injections, Intraperitoneal
  • Male
  • Melatonin / pharmacology*
  • Rats
  • Rats, Wistar
  • Receptors, Cell Surface / antagonists & inhibitors
  • Receptors, Cell Surface / physiology
  • Receptors, Cytoplasmic and Nuclear / antagonists & inhibitors
  • Receptors, Cytoplasmic and Nuclear / physiology
  • Receptors, Melatonin
  • Receptors, Serotonin / drug effects
  • Receptors, Serotonin / physiology
  • Serotonin / pharmacology
  • Serotonin / physiology
  • Serotonin Receptor Agonists / pharmacology
  • Sexual Behavior, Animal / drug effects*
  • Synaptic Transmission / physiology
  • Tryptamines / pharmacology


  • Amphetamines
  • Receptors, Cell Surface
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Melatonin
  • Receptors, Serotonin
  • Serotonin Receptor Agonists
  • Tryptamines
  • luzindole
  • Serotonin
  • Melatonin
  • 4-iodo-2,5-dimethoxyphenylisopropylamine