Kennaway D J, Rowe S A, Ferguson S A
Department of Obstetrics and Gynaecology, University of Adelaide, Medical School, Adelaide, Australia.
Brain Res. 1996 Oct 21;737(1-2):301-7. doi: 10.1016/0006-8993(96)00922-5.
The effect of serotonin agonists on the rhythmic excretion of the melatonin metabolite 6-sulphatoxymelatonin was examined in rats. The animals were maintained in 12L:12D and administered saline, quipazine (10 mg/kg), (+/-)-2-propylamino-8-hydroxy-1,2,3,4-tetrahydronaphthalene hydrobromide (8-OH-DPAT, 5 mg/kg) or buspirone (10 mg/kg), 4 h after dark (ZT16). All three drugs caused an acute, transient suppression of 6-sulphatoxymelatonin excretion and a significant delay (P < 0.01) in the onset of the nocturnal rise on the following night of 2.1 +/- 0.6, 1.4 +/- 0.7 and 1.5 +/- 0.3 h respectively while saline administration had no effect (0.4 +/- 0.2 h delay, P > 0.01). To examine the effects of the time of day of agonist administration, groups of rats were treated with quipazine (10 mg/kg) or 8-OH-DPAT (5 mg/kg) 18, 24 or 30 h after the initiation of continuous darkness (CT6, CT12 or CT18) and monitored for a further two nights. Quipazine but not 8-OH-DPAT injection at CT6 resulted in a small but significant delay in the onset of 6-sulphatoxymelatonin excretion on the following night (1.0 +/- 0.2 h and 0.3 +/- 0.2 h) while treatment with both agonists at CT12 failed to affect the onset of excretion (0.8 +/- 0.2 and 0.1 +/- 0.2 h). When quipazine (10 mg/kg) was administered at CT18, 6-sulphatoxymelatonin excretion was acutely suppressed for the rest of the night and there was a large significant delay in the onset of 6-sulphatoxymelatonin excretion (1.2 +/- 0.2 h) while a smaller delay was observed following 8-OH-DPAT administration (0.8 +/- 0.2 h). The acute suppression of 6-sulphatoxymelatonin excretion and subsequent phase delay following quipazine treatment at CT18 was also evident at doses of 1 mg/kg (1.6 +/- 0.4 h) and 3 mg/kg (1.5 +/- 0.6 h). These results show that peripheral administration of serotonin agonists active at 5HT1a/5HT7 receptors mimic the dual effects of light on melatonin production in the rat and raise the possibility that serotonin pathways are more important in mediating the effects of retinally perceived light in the rat than previously believed.
在大鼠中研究了血清素激动剂对褪黑素代谢物6-硫酸氧褪黑素节律性排泄的影响。将动物饲养在12小时光照：12小时黑暗的环境中，并在黑暗开始4小时后（ZT16）给予生理盐水、喹哌嗪（10毫克/千克）、（±）-2-丙基氨基-8-羟基-1,2,3,4-四氢萘氢溴酸盐（8-OH-DPAT，5毫克/千克）或丁螺环酮（10毫克/千克）。所有这三种药物均导致6-硫酸氧褪黑素排泄的急性、短暂抑制，并且在接下来的夜晚夜间升高的开始时间分别显著延迟（P<0.01）2.1±0.6小时、1.4±0.7小时和1.5±0.3小时，而给予生理盐水则没有效果（延迟0.4±0.2小时，P>0.01）。为了研究激动剂给药时间的影响，在持续黑暗开始后18、24或30小时（CT6、CT12或CT18）用喹哌嗪（10毫克/千克）或8-OH-DPAT（5毫克/千克）处理大鼠组，并再监测两个夜晚。在CT6注射喹哌嗪而非8-OH-DPAT导致接下来夜晚6-硫酸氧褪黑素排泄开始时间有小但显著的延迟（1.0±0.2小时和0.3±0.2小时），而在CT12用两种激动剂处理均未影响排泄开始时间（0.8±0.2小时和0.1±0.2小时）。当在CT18给予喹哌嗪（10毫克/千克）时，6-硫酸氧褪黑素排泄在当晚剩余时间被急性抑制，并且6-硫酸氧褪黑素排泄开始时间有大的显著延迟（1.2±0.2小时），而给予8-OH-DPAT后观察到较小的延迟（0.8±0.2小时）。在CT18用喹哌嗪处理后6-硫酸氧褪黑素排泄的急性抑制和随后的相位延迟在1毫克/千克（1.6±0.4小时）和3毫克/千克（1.5±0.6小时）剂量时也很明显。这些结果表明，在5HT1a/5HT7受体上起作用的血清素激动剂外周给药模拟了光对大鼠褪黑素产生的双重作用，并增加了血清素途径在介导大鼠视网膜感知光的作用中比以前认为的更重要的可能性。
