Effects of electroconvulsive shock on the levels of biogenic amines and their metabolites in rat brain

의학과/박사[한글] 전기경련 요법이 우울증, 특히 심한 망상성 우울증, 내인성 우울증, 혹은 자살의도를 동반한 우울증에 효과적이라고 알려져 있으며 그 작용기전으로 신경전달물질이나 신경조정 인자에 영향을 줄 것이라 추측되고 있다. 최근의 연구에 의하면 반복적인 전기경련 충격으로 뇌내의 norepinephrine, dopamine 또는 5-hydroxytryptamine (5-HT) 등의 biogenic amine이 변동된다고 하며 그 외에도 acetylcholine, y-aminobutyric acid 및 opioid peptide등의 관련설이 대두되고 있다. 그러나 대부분의 실험들이 한가지 amine의 변동만을 검색하여 전반적인 뇌기능을 유기적으로 추구하지 못한 상태이다. 따라서 이번 실험에서는 흰쥐에서 전기 경련 충격을 1회 또는 48시간 간격으로 6회 반복 시행하여 뇌척수액 및 뇌조직의 여러 부위 (전두피질,선조체,해마, 시상,시상하부)에서 norepinephrine, epinephrine, dopamine 및 5-HT와 대사산물인 3, 4-dihydroxyphenylacetic acid(DOPAC),homovanillic acid (HVA) 및 5-hydroxyindoleacetic acid (5-HIAA)를 high performance liquid chromatography-electrochemical detector (HPLC-ECD)로 측정하여 상호 연관성을 검색하였다. 실험성적을 요약하면 다음과 같다. 1. 정상 흰쥐의 뇌조직내 norepinephrine 단위함량은 시상하부에서 가장 높으며 dopamine, DOPAC 및 HVA는 선조체에서, 5-HT와 5-HIAA는 시상하부에서 가장 높고, epinephrine은 어느 부위에서도 검출되지 않았다. 2. 전기경련 충격 1회 시행으로 선조체에서 DOPAC함량이 감소하였고 dopamine함량이 증가되었으며 시상하부에서 5-HIAA 함량이 감소하였다. 3. 반복적인 전기경련 충격으로 전두피질의 norepinephrine이 감소하였다. 5-HT는 선조체에서 증가되나 시상하부에서 감소하였고, 5-HIAA는 전두피질과 선조체에서 증가되었다. 5-HIAA/5-HT 비율은 전두피질과 시상하부에서 증가되었으며 DOPAC은 시 상하부에서 감소하였다. 4. 뇌척수액에서는 DOPAC, 5-HIAA 및 HVA가 검출되고 반복적인 전기경련 충격으로 DOPAC이 증가하고 5-HIAA는 감소하나 일회 시행시에는 별다른 변동을 보이지 않았다. 이상의 성적으로 보아 전기경련 충격에 의한 뇌내 biogenic amino의 함량은 충격 횟수 및 뇌의 부위에 따라 다르나, 주로 5-HT에 영향을 주고, 또한 선조체와 시상하부의 dopamine 대사감소를 일으킴으로 보아 이와 같은 작용이 항우울 효과에 관여된다고 생각한다. [영문] Electroconvulsive therapy has been used in the treatment of major depression. Its effectiveness is estimated to be superior to that of tricyclic antidepressants, particularly in severe, delusional endogenous depressions with suicidal ideation. It is reported that electroconvulsive shock (ECS) affects a variety of putative neurotransmitters; norepinephrine, dopamine, serotonin, acetylcholine, γ-aminobutyric acid and endorphins. Since most studies were performed on whole brain or limited area of brain and measured only specific monoamine, changes in the levees of biogenic amines in discrete brain regions or difference between the regions might have been masked. The present investigation was undertaken to elucidate the effects of single or repeated ECS on the regional levels of biogenic amines in rat brain and cerebrospinal fluid. The male Sprague-Dawley rats were used. After single or repeated ECS, blocks of tissue were obtained from the frontal cortex, corpus striatum, hippocampus, thalamus, and hypothalamus, immediately after the collection of cerebrospinal fluid from cisterns magna. The concentration of biogenic imines (norepinephrine, dopamine, 5·hydroxytryptamine (5-HT)) and their metabolites (3,4-dihydroxyphenylacetic acid(DOPAC), homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA)) were measured by means of high performance liquid chromatography-electrochemical detector (HPLC·ECD). The results obtained are as follows: 1) In the normal rat, the concentration of norepinephrine was the highest in hypothalamus. Dopamine, DOPAC and HVA were highest in corpus striatum, and 5-HT and 5-HIAA were highest in hypothalamus. Epinephrine was not detectable in any part of the brain tissue nor in cerebrospinalfluid. 2) In single ECS group, the concentration of DOPAC was decreased and that of dopamine was increased in corpus striatum. 5- HIAA was decreased in hypothalamus by single ECS. 3) In case of repeated ECS. the concentration of norepinephrine was decreased in frontal cortex and that of DOPAC was decreased in hypothalamus. 5-HT was increased in striatum and decreased in hypothalamus. and 5-HIAA was increased in frontal cortx and corpus striatum. The ratio of 5-HIAA/5-HT was increased in all brain region tested, especially in frontal cortex and hypothalamus by repeated ECS. 4) In cerebrospinal fluid, DOPAC, 5.HIAA and HVA were detectable. While single ECS did not change the concentration 7f these metabolites, repeated ECS increased DOPAC and decreased5. HIAA. These results indicate that the effects of ECS on biogenic amines and their metabolites differ to the frequency of ECS and the legions of rat brain. And it is conceivable that the change in 5-HT metabolism is the main effect of repeated ECS and, in part, decreased metabolism of dopamine in corpus stri atum and hypothalamus contributes to the antidepressive effect of ECS.restrictio