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NMDA receptor antagonists block the effects of light on circadian behavior in the mouse
C S Colwell1, R G Foster, M Menaker
1Department of Biology, University of Virginia, Charlottesville 22901.
Abstract:
We report here the results of experiments designed to evaluate whether NMDA receptors mediate the phase shifting effects of light on the circadian rhythm of wheel-running activity in mice. Intraperitoneal administration of either the non-competitive NMDA receptor antagonist, (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,b]cyclohepten-5,10-imine maleate (MK-801), or the competitive NMDA receptor antagonist, 3(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) blocked light-induced phase advances and delays. Neither drug, by itself, caused any consistent effect on the phase of the rhythm. Furthermore, there was no significant difference between the effects of MK-801 on light-induced phase shifts in a retinally degenerate and retinally normal strain of C57 mouse. These data, coupled with previous findings, indicate that excitatory amino acid receptors play an important role in the transmission of light information from the retina to the circadian system.
Insights
NMDA receptors are crucial for how light shifts the mouse circadian rhythm. Blocking these receptors with MK-801 or CPP prevented light-induced phase changes in wheel-running activity.
Area of Science:
- Neuroscience
- Chronobiology
- Molecular Biology
Background:
- The circadian rhythm regulates physiological processes over a 24-hour cycle.
- Light is a primary environmental cue for synchronizing circadian rhythms.
- The role of NMDA receptors in mediating light's effects on circadian rhythms is not fully understood.
Purpose of the Study:
- To investigate whether NMDA receptors are involved in mediating the phase-shifting effects of light on the circadian rhythm of wheel-running activity in mice.
- To determine if blocking NMDA receptors affects light-induced phase advances and delays.
Main Methods:
- Mice were administered intraperitoneally with NMDA receptor antagonists: MK-801 (non-competitive) and CPP (competitive).
- Light pulses were administered to induce phase shifts in wheel-running activity.
- The effects of antagonists on light-induced phase shifts were compared to control groups.
- Experiments included comparisons between retinally degenerate and normal mouse strains.
Main Results:
- Both MK-801 and CPP significantly blocked light-induced phase advances and delays in circadian rhythm.
- Neither antagonist alone altered the phase of the circadian rhythm.
- The effects of MK-801 were consistent across retinally degenerate and normal C57 mouse strains.
Conclusions:
- NMDA receptors play a significant role in transmitting light information from the retina to the circadian system.
- Excitatory amino acid receptors, including NMDA receptors, are critical components of the photic entrainment pathway.
- These findings support the involvement of NMDA receptor signaling in the neural circuitry underlying circadian photoentrainment.