A 5-HT(1B) receptor agonist inhibits light-induced suppression of pineal melatonin production.
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.
Rea
M A
MA
BRAIN Research Institute, Air Force Research Laboratory, Brooks AFB, TX, USA. mrea@uh.edu
Pickard
G E
GE
D000818:Animals; D002940:Circadian Rhythm / Q000187:drug effects; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D008297:Male; D008550:Melatonin / Q000096:biosynthesis*; D008647:Mesocricetus; D008719:Methiothepin / Q000494:pharmacology; D010775:Photic Stimulation; D010870:Pineal Gland / Q000187:drug effects* / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin / Q000502:physiology*; D012160:Retina / Q000502:physiology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013493:Suprachiasmatic Nucleus / Q000502:physiology; D014795:Visual Pathways
D010879:Piperazines; D011725:Pyridines; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C018406:1-(3-trifluoromethylphenyl)piperazine; D008719:Methiothepin; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D008550:Melatonin