A 5-HT1B receptor agonist inhibits light-induced suppression of pineal melatonin production

Abstract Serotonin (5-HT) modulates the phase adjusting effects of light on the mammalian circadian clock through the activation of presynaptic 5-HT 1B receptors located on retinal terminals in the suprachiasmatic nucleus (SCN). The current study was conducted to determine whether activation of 5-HT 1B receptors also alters photic regulation of nocturnal pineal melatonin production. Systemic administration of the 5-HT 1B receptor agonist TFMPP attenuated the inhibitory effect of light on pineal melatonin synthesis in a dose-related manner with an apparent ED 50 value of 0.9 mg/kg. The effect of TFMPP on light-induced melatonin suppression was blocked by the 5-HT 1 receptor antagonist, methiothepin, but not by the 5-HT 1A antagonist, WAY 100,635, consistent with the involvement of 5-HT 1B receptors. The results are consistent with the interpretation that activation of presynaptic 5-HT 1B receptors on retinal terminals in the SCN attenuates the effect of light on pineal melatonin production, as well as on circadian phase.