RED-LIGHT-INDUCED SUPPRESSION OF MELATONIN SYNTHESIS IS MEDIATED BY N-METHYL-D-ASPARTATE RECEPTOR ACTIVATION IN RETINALLY NORMAL AND RETINALLY DEGENERATE RATS

Pineal gland N-acetyltransferase (NAT) activity and pineal and serum l evels of melatonin declined linearly in albino rats acutely exposed to different intensities of red light (600 nm or higher; low, 140 mu W/c m(2); moderate, 690 mu W/cm(2); high, 1200 mu W/cm(2)) during the midd le of the night. The high intensity red light was as effective as whit e light (780 mu W/cm(2)) in suppressing NAT activity and pineal and ci rculating melatonin. Red-light-inhibited nighttime NAT activity and su ppressed nocturnal melatonin levels in both retinally degenerate and n ormal rats. Pretreatment with the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 (10 mg/kg intraperitoneally) completely prevented t he red-light-induced inhibition of nighttime melatonin synthesis. Magn esium chloride (300 mg/kg intraperitoneally) reduced the inhibitory ef fects of low and moderate intensities of red light but was ineffective when high red-light intensity was used. However, both agents failed t o antagonize the suppression of nighttime melatonin synthesis elicted by the exposure to white light. Since retinally degenerate and retinal ly normal animals respond in the same way to both red-light and pharma cological intervention with the NMDA receptor blocker MK-801, the find ings indicate that the activation of central hypothalamic NMDA recepto rs might mediate the photic inhibition of nocturnal melatonin synthesi s in the pineal gland elicited by the exposure to red light at night. Red-light-induced suppression of nocturnal melatonin synthesis possibl y can be used to investigate the biochemical mechanisms by which light entrains melatonin synthesis and to study the pharmacological and phy siological effects of endogenous and synthetic agents that antagonize the NMDA receptor response. (C) 1995 John Wiley & Sons, Inc.