Butler M O, Morinobu S, Duman R S
Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut.
J Neurochem. 1993 Oct;61(4):1270-6. doi: 10.1111/j.1471-4159.1993.tb13618.x.
The present study examines the influence of electroconvulsive seizure (ECS), as well as antidepressant drugs, on levels of serotonin2 (5-HT2) receptor mRNA in rat frontal cortex. Using a sensitive RNase protective assay, preliminary studies demonstrated the predicted regional distribution for the 5-HT2 receptor mRNA: levels of 5-HT2 mRNA were highest in frontal cortex (2.58 amol/micrograms of total RNA), intermediate in neostriatum, thalamus, and midbrain, and lowest in hippocampus, cerebellum, and choroid plexus. Chronic (10 or 14 days), but not acute (1 or 3 days), ECS treatment significantly increased levels of 5-HT2 receptor mRNA. ECS treatment resulted in a similar time-dependent up-regulation of 5-HT2 receptor ligand binding; chronic, but not acute, ECS treatment significantly increased levels of [3H]ketanserin ligand binding, confirming previous reports. Northern blot analysis demonstrated that 5-HT2 receptor mRNA occurs as two bands (approximately 5 and 6 kb in size), both of which were increased by chronic ECS treatment. The influence of antidepressant drug treatments on 5-HT2 receptor mRNA was also examined. Chronic fluoxetine treatment increased levels of 5-HT2 receptor mRNA, although levels of [3H]ketanserin ligand binding were not altered. In contrast, chronic administration of imipramine, mianserin, and tranylcypromine, treatments that decreased ligand binding, did not decrease levels of 5-HT2 receptor mRNA. In fact, mianserin treatment caused a small, but significant, increase in levels of receptor mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)
本研究探讨了电惊厥发作(ECS)以及抗抑郁药物对大鼠额叶皮质中5-羟色胺2(5-HT2)受体mRNA水平的影响。通过一种灵敏的核糖核酸酶保护分析方法,初步研究证实了5-HT2受体mRNA的预期区域分布:5-HT2 mRNA水平在额叶皮质中最高(2.58 amol/微克总RNA),在新纹状体、丘脑和中脑居中,而在海马体、小脑和脉络丛中最低。慢性(10或14天)而非急性(1或3天)的ECS治疗显著提高了5-HT2受体mRNA水平。ECS治疗导致5-HT2受体配体结合呈现类似的时间依赖性上调;慢性而非急性的ECS治疗显著提高了[3H]酮色林配体结合水平,证实了先前的报道。Northern印迹分析表明,5-HT2受体mRNA以两条带(大小约为5和6 kb)的形式出现,慢性ECS治疗均使其增加。还研究了抗抑郁药物治疗对5-HT2受体mRNA的影响。慢性氟西汀治疗提高了5-HT2受体mRNA水平,尽管[3H]酮色林配体结合水平未改变。相比之下,慢性给予丙咪嗪、米安色林和反苯环丙胺这些降低配体结合的治疗方法,并未降低5-HT2受体mRNA水平。事实上,米安色林治疗使受体mRNA水平有小幅但显著的升高。(摘要截选至250词)