실험적 알콜중독이 biogenic amine대사에 미치는 영향

Abstract

[영문]

[한글]

알콜섭취로 인한 생리적 반응과 행동학적 변화는 대부분 뇌내의 신경전달 물질 변동에

연유되며, 이때 뇌의 신경전달물질중 특히 5-hydroxytryptamine과 catecholamines함량 및

그 대사산물이 주목되어 왔으나 정확한 양상은 아직 확실하지 않다.

이번 실험에서는 흰쥐를 사용하여 실험적으로 급성 또는 만성 알콜중독 상태를 유발시

켜 이때의 뇌내 biogenic amines의 함량 및 대사변동을 관찰하였다. 동일한 실험동물에서

뇌척수액과 뇌의 부위별 조직 (전두피질, 선조체, 해마, 시상, 시상하부. 흑질, 소뇌)을

적출하였으며 조직내의 norepinephrine, epinephrine, dopamine 및 5-hydroxytryptamine

(5-HT)과 그의 주요대사산물인 3-methoxy-4-hydoxyphenylethylene glycol(MOPEG), homova

nillic acid(HVA), 5-hydroxyindoleacetic acid(5-HIAA)들의 함량을 LCEC system을 이용

하여 측정하였다.

실험성적을 요약하면 다음과 같다.

1. 흰쥐의 뇌조직내 norepinephrine과 5-HT의 단위함량은 시상하부에서 가장 많았고 do

pamine함량은 선조체에서 가장 많았다. HVA는 선조체에서만 검출되었으며 epinephrine은

어느 조직에서도 검출되지 않았다.

2. 급성 알콜중독 당시 5-HT함량이 시상에서, 5-HIAA함량이 시상하부에서 증가되었고,

norepinephrine함량은 소뇌에서 증가되었다.

3. 만성 알콜중독으로는 5-HT함량이 시상과 시상하부에서, 5-HIAA함량이 해마, 시상,

시상하부 및 소뇌에서 증가되었고 norepinephrine함량은 시상하부에서 증가되었다.

4. 뇌척수액에서는 5-HIAA와 HVA만이 검출되었으며 만성 알콜중독으로 5-HIAA함량이 증

가되었다.

이상의 성적으로 보아 급성 또는 만성 알콜중독은 뇌조직내 biogenic amines와 그 대사

산물의 함량에 심한 변동을 초래함을 알 수 있었으며 특히 5-HT와 norepinephrine은 알콜

의 약리학적 반응 및 행동변화에 관여한다고 생각된다.

Effect of Experimental Ethanol Intoxication on the Levels of Biogenic Amines and

Their Metabolites in Rat Brain

Young Jin Kim

Department of Medical Science The Graduate School, Yonsei University

(Directed by Professor Sa Suk Hong, M.D.)

It is generally assumed that many of the pharmacological and behavioral effects

of acute and chronic ethanol intoxication are the result of changes of

neurotransmitter systems in brain. Among the many neurotransmitters examined upon

alcohol intoxication, particular attention has been focused on the

5-hydroxytryptamine(5-HT) and catecholamines. However, the effect of ethanol

administration on the levels of these biogenic amines in various parts of the brain

is not clear. Present investigation was undertaken to elucidate the effect of the

ethanol intoxication on the levels of these biogenic amines in brain tissues and

cerebrospinal fluid.

The albino rats of either sex were used. Under hexobarbital anesthesia,

immediately after collection of cerebrospinal fluid from cisterna magna, blocks of

tissue were obtained from the frontal cortex, corpus striatum, hippocampus,

thalamus, hypothalamus, substantia nigra and cerebellum. The concentrations of

biogenic amines (norepinephrine, epinephrine, dopanine, 5-HT) and their metabolites

[3-methoxy-4-hydroxyphenylethylene glycol (M0PEG), homovanillic acid (HVA),

5-hydroxyindoleacetic acid (5-HIAA)] in brain tissues and cerebrospinal fluid were

detected by employing LCEC.

The results obtained are as follows.

1. In the brain of untreated normal rat, concentrations of norepinephrine and

5-HT were the highest in hypothalamus and that of dopamine was the highest in

corpus striatum. HVA was not detectable except in corpus striatum. Epinephrine was

not detectable in any parts of brain tissues and cerebrospinal fluid.

2. Acute ethanol intoxication increased the concentration of 5-HT in thalamus,

5-HIAA in hypothalamus and norepinephrine in cerebellum.

3. Upon chronic alcohol intoxication, the concentrations of 5-HT were increased

in thalamus and hypothalamus and those of 5-HIAA were increased in hippocampus,

thalamus, hypothalamus and cerebellum. However, the concentration of norepinephrine

was increased only in hypothalamus.

4. In cerebrospinal fluid, only 5-HIAA and HVA were detectable and the

concentrationo of 5-HIAA was increased upon chronic ethanol intoxication.

By theme findings it is clear that either the acute or chronic ethanol

intoxication has caused significant changes in the levels of brain biogenic amines

and of their metabolites. And it is suggested that the changes in the 5-HT in

hippocampus, thalamus, hypothalamus and cerebellum and the levels of norepinephrine

in hypothalamus and cerebellum are the targets of acute or chronic ethanol

intoxication.