Rowe S A, Kennaway D J
Department of Obstetrics and Gynaecology, University of Adelaide, Medical School, South Australia.
Brain Res Bull. 1996;41(6):351-8. doi: 10.1016/s0361-9230(96)00189-x.
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.
利用NMDA受体拮抗剂MK - 801在大鼠中研究了兴奋性氨基酸作为光对松果体褪黑素分泌的急性抑制及随后延迟效应的介导物质的可能作用。在暗期开始4小时后，于15分钟的光脉冲（200勒克斯）前15分钟腹腔注射生理盐水或剂量高达3毫克/千克的MK - 801，并测定6 - 硫酸氧褪黑素（aMT.6S）的排泄量。在这些条件下，注射生理盐水/暴露于光下的动物表现出尿中aMT.6S排泄的急性、完全但短暂的抑制，以及次日夜晚aMT.6S排泄开始延迟1.5±0.2小时。MK - 801未能阻断光的急性或相位延迟效应（开始延迟2.2±0.4小时）。在脉冲前15分钟用MK - 801（3毫克/千克）预处理未能阻断较短、强度较低的光脉冲的效应（例如，1分钟/2勒克斯；注射生理盐水后开始延迟2.0±0.4小时，注射MK - 801后为1.5±0.1小时），或在短持续时间低强度脉冲前60分钟的效应。在其他实验中，在熄灯时或暗期开始4小时后于黑暗中注射MK - 801（1和3毫克/千克）未能影响aMT.6S的排泄。在熄灯时或黑暗后4小时注射NMDA（10和30毫克/千克），并未通过降低aMT.6S排泄或导致次日夜晚排泄开始延迟来模拟光脉冲的效应。最后，在暗期开始4小时后注射MK - 801（3毫克/千克）未能阻断15分钟光脉冲（200勒克斯）对大鼠活动的相位延迟效应。这些结果不支持如下假说：视网膜 - 下丘脑束中作用于NMDA受体亚型并终止于视交叉上核的兴奋性氨基酸介导了光对大鼠松果体褪黑素和活动节律的影响。
