Enhancement of melatonin's antigonadal action by daily injections of the serotonin uptake inhibitor fluoxetine in male hamsters.

The antigonadal effects of daily melatonin injections in golden hamsters are known to be dependent on the time of day when injections are given. As the serotonergic system of the brain has been shown to undergo daily variations, and to influence gonadotrophic activity, it was decided to investigate the relationship between melatonin effects and brain serotonergic function by employing the selective inhibitor of serotonin uptake fluoxetine (Lilly 110140). Daily injections of fluoxetine (5 mg/kg) were administered at two different times of day (late scotophase or late photophase) in combination with or without melatonin (25 micrograms) at either early or late photophase. Following nine weeks on a long photoperiod (14L/10D) testicular widths and weights in all groups receiving late-photophase melatonin were significantly diminished. Average testicular widths and weights in groups receiving fluoxetine plus late-photophase melatonin were smaller than those groups receiving late-photophase melatonin alone. Furthermore, animals receiving fluoxetine plus early-photophase melatonin also showed signs of gonadal regression. These results support the hypothesis that altered serotonergic function is a component of melatonin-induced gonadal inhibition in the male hamster.