Red‐light‐induced suppression of melatonin synthesis is mediated by N‐methyl‐D‐aspartate receptor activation in retinally normal and retinally degenerate rats

Abstract

Pineal gland N-acetyltransferase (NAT) activity and pineal and serum levels of melatonin declined linearly in albino rats acutely exposed to different intensities of red light (600 nm or higher; low, 140 microW/cm2; moderate, 690 microW/cm2; high, 1200 microW/cm2) during the middle of the night. The high intensity red light was as effective as white light (780 microW/cm2) in suppressing NAT activity and pineal and circulating melatonin. Red-light-inhibited nighttime NAT activity and suppressed nocturnal melatonin levels in both retinally degenerate and normal rats. Pretreatment with the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 (10 mg/kg intraperitoneally) completely prevented the red-light-induced inhibition of nighttime melatonin synthesis. Magnesium chloride (300 mg/kg intraperitoneally) reduced the inhibitory effects of low and moderate intensities of red light but was ineffective when high red-light intensity was used. However, both agents failed to antagonize the suppression of nighttime melatonin synthesis elicted by the exposure to white light. Since retinally degenerate and retinally normal animals respond in the same way to both red-light and pharmacological intervention with the NMDA receptor blocker MK-801, the findings indicate that the activation of central hypothalamic NMDA receptors might mediate the photic inhibition of nocturnal melatonin synthesis in the pineal gland elicited by the exposure to red light at night. Red-light-induced suppression of nocturnal melatonin synthesis possibly can be used to investigate the biochemical mechanisms by which light entrains melatonin synthesis and to study the pharmacological and physiological effects of endogenous and synthetic agents that antagonize the NMDA receptor response.

Spectral and duration sensitivity to light-at-night in ‘blind’ and sighted rodent species

“…At long wavelengths, previously published data are often contradictory regarding the inhibitory effects of LAN in some rodent species (Vanecek and Illnerova, 1982;Poeggeler et al, 1995;Hanifin et al, 2006), and in some data there is a lack of a well-defined pattern of effects (Cardinali et al, 1972;Brainard et al, 1984;Benshoff et al, 1987). Our results demonstrated no clear sensitivity in MLT levels of M. socialis to LAN at 679nm (red), indicating a marginal role for red-shifted retinal photoreceptors, such as NIFPRs, ) at three different wavelengths at increasing durations of acclimation (1day, 1week and 3weeks) starting from control levels.…”

Melatonin Sensitivity to Dim White Light in Affective Disorders

“…The neuronal pathway from the retina to the SCN (via the retinohypothalamic tract) mediates the suppressive effect of light and the entrainment of the melatonin rhythm to the light/dark cycle (Moore and Lenn 1972). Previous studies have indicated that excitatory amino acids may be involved in photic entrainment of circadian rhythms and melatonin production (Cowell et al 1991;Ohi et al 1993;Poeggeler et al 1995). Further studies have shown that glutamate, the dominant excitatory neurotransmitter in the central nervous system, mediates photic entrainment (DeVries et al 1993).…”

“…Pharmacological studies have revealed that antagonists of postsynaptic receptors that mediate the actions of this neurotransmitter block the light induced suppression of melatonin (Cowell et al 1991;Ohi et al 1993). Hypothalamic N -methyl-D -aspartate (NMDA) receptors coupled to a nitric oxide/cGMP signaling pathway have been identified (Amir 1992;Cowell et al 1990;Mikkelsen et al 1995;Poeggeler et al 1995). The observed supersensitivity to light in patients with BD and SAD may thus be related to a NMDA receptor mediated mechanism.…”

Subsensitive melatonin suppression by dim white light: possible biological marker of panic disorder

“…Previous studies have indicated that excitatory amino acids may be involved in photic entrainment of circadian rhythms and melatonin production (Cowell et al, 1990 ;Mikkelsen et al, 1995 ;Ohi et al, 1993 ;Poeggeler et al, 1995). Further studies have shown that glutamate, the dominant excitatory neurotransmitter in the central nervous system mediates photic entrainment (DeVries et al, 1993).…”