EFFECTS OF SINGLE AND CHRONIC TREATMENT WITH TRANYLCYPROMINE ON EXTRACELLULAR SEROTONIN IN RAT-BRAIN
EFFECTS OF SINGLE AND CHRONIC TREATMENT WITH TRANYLCYPROMINE ON EXTRACELLULAR SEROTONIN IN RAT-BRAIN
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DOI：
10.1016/0014-2999(94)90717-x
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发表时间：
1994-10-03
影响因子：
5
通讯作者：
ARTIGAS, F
中科院分区：
文献类型：
--
作者：
FERRER, A;ARTIGAS, F
用微透析技术观察了抗抑郁药反苯环丙胺对清醒大鼠额叶皮质和中缝背核组织和细胞外5-羟色胺（5-HT）和5-羟吲哚乙酸（5-HIAA）含量的影响。用硫酸反苯环丙胺（0.5、3和15 mg/kg，i. p.）剂量依赖性升高透析液5-HT在这两个领域，但更显着的DRN。细胞外和组织5-HT浓度的影响，药物以不同的方式。前者在组织5-HT达到平台时急剧增加。这可能反映了细胞内储存的饱和和胺的溢出。相反，组织和细胞外5-HIAA浓度-表明反苯环丙胺的代谢作用-受到类似的影响。用0.5mg/kg.day的反苯环丙胺硫酸盐治疗2周增加了额叶皮质和中缝背核中的基础细胞外5-HT（约100 mg/kg）。220%），而进一步注射0.5 mg/kg在这两个区域均无影响。因此，用低剂量反苯环丙胺进行慢性而非急性治疗会增加细胞外5-HT浓度，这表明这种单胺氧化酶抑制剂的临床作用与其增强5-羟色胺能传递的能力有关。
We have examined the effects of tranylcypromine, a monoamine oxidase inhibitor used as antidepressant, on the tissue and extracellular concentration of serotonin (5-hydroxytryptamine, 5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in frontal cortex and dorsal raphe nucleus using microdialysis in conscious rats. Single treatment with tranylcypromine sulphate (0.5, 3 and 15 mg/kg, i.p.) dose dependently elevated dialysate 5-HT in both areas but more markedly in the DRN. Extracellular and tissue 5-HT concentrations were affected by the drug in a different manner. The former increased sharply when tissue 5-HT reached a plateau. This may have reflected saturation of intracellular stores and overflow of the amine. In contrast, tissue and extracellular 5-HIAA concentrations - that indicate metabolic effects of tranylcypromine - were affected similarly. A 2-week treatment with 0.5 mg/kg.day of tranylcypromine sulphate increased basal extracellular 5-HT in frontal cortex and dorsal raphe nucleus (ca. 220%) whereas a further injection of 0.5 mg/kg was without effect in both areas. Thus, chronic, but not acute, treatment with low doses of tranylcypromine increases extracellular 5-HT concentration, suggesting that clinical effects of this monoamine oxidase inhibitor are related to its capacity to enhance serotonergic transmission.