삼환 항우울제가 뇌내 Biogenic amine 함량에 미치는 영향

Abstract

[한글]

삼환 항우울제 투여로 뇌수의 biogenic amine황성이 항진된다는 것은 대체로 인정되나, 대부분의 실험이 뇌조직 전체 또는 어느 한 부위를 대상으로 하고 또한 특정 amine만을 검색하여 전반적인 뇌기능을 유기적으로 추구하지 못하고 있는 실정이다.

이번 실험에서는 삼환 항우울제인 imipramine 및 desipramine을 일회 또는 장기간 흰쥐에 투여하여 뇌내 biogenic amine과 그 대사산물의 함량변동을 관찰하였다. 동일한 실험동물에서 뇌척수액과 뇌의 부위별 조직 (전두피질, 선조체, 해마, 시상, 시상하부, 혹질, 소뇌)을 적출하여 norepinephrine, epinephrine, dopamine 및 5-hydroxytryptamine (5-HT) 과 대사산물인 dihydroxyphenylacetic acid(DOPAC), homovanillic acid(HVA) 및 5-hydroxyindoleacetic acid(5-HIAA ) 를 High Performance Liquid Chromatography·Electrochemical Detector(HPLC-ECD)로 측정하고 상호 연관성을 검색하였다.

실험성적을 요약하면 다음과 같다.

1. 정상 흰쥐의 뇌조직내 norepinephrine 단위함량은 시상하부에서 가장 높았으며 dopamine, DOPAC 및 HVA는 선조체에서, 5-HT와 5·HIAA는 흑질에서 가장 높았고 epinephrine은 어느 부위에서도 검출되지 않았다.

2. Imipramine 일회투여로 시상하부, 선조체, 전두피질, 혹질 및 시상에서 5·HIAA 함량이 감소되었고, 선조체의 DOPAC 함량도 감소되었다. 장기투여로는 biogenic amino 및 대사산물함량이 대조군과 비슷하였으나 선조체의 DOPAC 함량은 감소되었다.

3. Desipramine 일회투여로는 뇌내 biogenic amine 및 대사산물 함량변동이 경미하나 전두피질에서 5·HIAA 함량이, 선조체에서 DOPAC 함량이 감소되었다. 장기투여로는 시상, 해마, 흑질, 전두피질, 시상하부에서 norepinephrine 함량이 감소하였으며 선조체에서 DOPAC 함량이 감소되었다.

4. 뇌척수액에서는 5·HIAA와 HVA 만이 검출되었으며 imipramine 또는 desipramine투여로 변동이 없었다.

이상의 성적으로 보아 삼환 항우울제 투여에 의한 뇌내 biogenic amine 함량변동은 투여약물 및 뇌의 부위에 따라 다르나, imipramine은 5-HT에, desipramine은 norepinephrine에 주로 영향을 주어 항우울 작용에 관계하고, 또한 선조체의 dopamine 대사감소도 항우울 작용에 일부 관여된다고 생각한다.

[영문]

It is generally accepted that the activity of biogenic amines is affected by tricyclic antidepressants. However, since most studies were performed on whole brain or limited area of brain and measured only specific monoamines, changes in the levels of biogenic amines in discrete brain regions or difference between the regions might have been masked.

Present investigation was undertaken to elucidate the effect of acute or chronic treatment with tricyclic antidepressants on the regional levees of biogenic amines in brain and cerebrospinal fluid.

The male Sprague-Dawley fats were used. After single or 3 weeks'treatment with imipramine or desipramine, blocks of tissue were obtained from the frontal cortex, corpus striatum, hippocampus, thalamus, hypothalamus, substance nigra and cerebellum immediate after collection of cerebrospinal fluid from cisterna magna. The concentration of biogenic amines and their metabolites(norepinephrine, epinephrine, dopamine, 5-hydfoxytryptamine (5-HT), dihydroxyphenylacetic acid(DOPAC), homovanillic acid(HVA), 5-hydroxyindoleacetic acid (5-HIAA)in brain tissues and cerebrospinal fluid were measured by means of High Performance Liquid Chromatography-Electroshemical Detector(HPLC-ECD).

The results obtained are as follows.

1. In the brain of normal rat, the concentration of norepinephrine was the highest in hypothalamus and those of dopamine, DOPAC, and HVA were the highest in corpus striatum, and those of 5-HT and 5-HIAA were the highest in substantia nigra. Epinephrine was not detectable in any part of the brain tissues nor in cerebrospinal fluid.

2. Single administration of imipramine decreased the concentration of 5-HIAA in hypo-thalamus, corpus striatum, frontal cortex, substantia nigra and thalamus, and that of DOPAC in corpus striatum. Chronic imipramine treatment decreased the concentration of DOPAC only in corpus striatum.

3. Single administration of desipramine decreased the concentration of 5-HIAA in frontal cortex and that of DOPAC in corpus striatum. Chronic desipramine treatment decreased the concentration of norepinephrine in thalamus, hippocampus, substantia nigra, frontal cortex and hypothalamus, and that of DOPAC in corpus striatum.

4. In cerebrospinal fluid only 5-HIAA and HVA were detectable and the concentration of these metabolites were not changed by the treatment with imipramine or desipramine.

These results indicate that the effects of single or chronic treatment with the tricyclic antidepressants on the biogenic amines and their metabolites differ to the regions of rat brain. And it is conceived that the treatment with imipramine affects mainly 5-HT metabolism, and that with desipramine affect mainly norepinephrine metabolism, and at least in part, decreased metabolism of dopamine in corpus striatum contributes to the antidepressant effeCt of these drugs.