Effect of NMDA receptor blockade on melatonin and activity rhythm responses to a light pulse in rats.

Abstract

The possible role of the excitatory amino acids as mediators of the acute suppression and subsequent delay by light of pineal melatonin production was studied in rats using the NMDA receptor antagonist MK-801. Saline or MK-801 in doses up to 3 mg/kg (IP), was administered 15 min before a 15-min light pulse (200 lx), 4 h after dark onset, and the excretion of 6-sulphatoxymelatonin (aMT.6S) determined. Under these conditions saline injected/light exposed animals exhibited an acute, total but transient suppression of urinary aMT.6S excretion and a delay in the onset of aMT.6S the following night of 1.5 +/- 0.2 h. MK-801 failed to block either the acute or phase delaying effect of light (onset delayed by 2.2 +/- 0.4 h). Pretreatment with MK-801 (3 mg/kg) failed to block the effects of shorter, less intense light pulses 15 min before the pulse (e.g., 1 min/2 lx; onset delayed by 2.0 +/- 0.4 h following saline, 1.5 +/- 0.1 h following MK-801) or 60 min before a short duration low intensity pulse. In other experiments MK-801 (1 and 3 mg/kg) failed to affect aMT.6S excretion when injected in the dark at the time of lights out or 4 h after dark onset. NMDA (10 and 30 mg/kg) injection at the time of lights out or 4 h after darkness did not mimic the effects of a light pulse by decreasing aMT.6S excretion or causing a delay in the onset of excretion the following night. Finally MK-801 (3 mg/kg) injected 4 h after dark failed to block the phase delaying effects of a 15 min light pulse (200 lx) on running activity in rats. These results do not support the hypothesis that excitatory amino acids in the retino-hypothalamic tract acting on the NMDA receptor subtype and terminating in the suprachiasmatic nucleus mediate the photic influences upon rat pineal melatonin and activity rhythms.