6-Hydroxydopamine 투여 흰쥐의 뇌중 Norepinephrine 함량에 대한 Nomifensine의 영향

Abstract

삼환계 항우울약이나 monoamine oxidase 억제약과 화학적으로 전혀 다른 tetrahydroisoquinoline계 항우울약인 nomifensine이 adrenaline성 효능신경에서 norepinephrine과 dopamine의 재도입을 억제한다고 보고 되어있다. 이러한 norepinephrine 재도입을 억제하는 약물에 의해 그 작용이 길항되는 6-hydroxydopamine을 갓 태어난 쥐에 피하주사하여 pons medulla와 대뇌피질에서 6-hydroxydoparnine에 의한 뇌 중 norepinephrine 변화에 미치는 nomifensine의 억제효과를 연구하고자 하였다. Norepinephrine의 재도입을 억제한다고 알려진 desipramine을 비교약물로 사용하였고 쥐는 주사한 후 7주만에 단두사혈하여 뇌 각 부위에서의 norepinephrine 함량을 측정하여 다음과 같은 결과를 얻었다. 1. 생후 첫째 날과 둘째 날 6-hydroxydopamine의 주사로 pons medulla의 norepinephrine함량은 증가되었고 대뇌피질에서는 norepinephrine이 고갈되었다.(P<0.001) 2. 생후 첫째 날과 둘째 날 6-hydroxydopamine 투여 30분전에 nomifensine 혹은 desipramine으로 전처리했을 때 pons mudulla에서 6-hydroxydopamine에 의한 norepinephrine 함량 증가가 길항되었다.(P<0.001) 3. 생후 첫째 날과 둘째 날 6-hydroxydopamine 투여 30분전에 nomifensine 혹은 desipramine으로 전처리했을 때 대뇌피질에서 6-hydroxydopamine에 의한 norepinephrine 고갈이 길항되였다.(P<0.001);Nomifensine, a tetrabydroisoquinoline antidepressant, has been reported to block the re-uptake of norepinephrine and dopamine. 6-hydroxydopamine was antagonized by a norepinephrine uptake inhibitor. Thus the present experiment was set up to investigate the effect of nomifensine on the change of brain norepinephrine induced by 6-hydroxydopamine, which was given systemically at birth, in pons medulla and cerebral cortex. And desipramine was compared because it is known to specifically inhibit the norepinephrine uptake in the brain. The rats were decapitated at 7th weeks after the injection and dissected to measure the norepinephrine content. The summarized results are as follows; 1. Administration of 6-hydroxydopamine 100mg/kg on day o and day 1 after birth increased norepinephrine contents in pons medulla and decreased in cerebral cortex. (P<0.001) 2. Administration of nomifensine 25mg/kg or desipramine 25mg/kg 1/2hr prior to each injection of 6-hydroxydopamine inhibited the increase of norepinephrine contents by 6-hydroxydopamine in pons medulla. (P<0.001) 3. Administration of nomifensine 25mg/kg or desipramine 25mg/kg 1/2hr prior to each injection of 6-bydroxydopamine inhibited the decrease of norepinephrine contents by 6-hydroxydopamine in cerebral cortex. (P<0.001)