NMDA 受體在D-cycloserine 對焦慮行為作用之角色

Effects of D-cycloserine on Anxiety Behavior: Role of NMDA Receptor

杜偉庭(Wei-Ting Tu) ； 曾鼎(Ting Tseng) ； 王安莉(An-Li Wang) ； 鍾宛玲(Wan-Ling Chung) ； 林俊成(Chun-Cheng Lin) ； 許立松(Li-Sung Hsu) ； 徐文鈺(Wen-Yu Hsu) ； 王慶福(Ching-Fu Wang) ； 何應瑞(Ying-Jui Ho)

《台灣醫學》 9卷2期 (2005/03) Pp. 173-179

https://doi.org/10.6320/FJM.2005.9(2).04

摘要

文獻指出麩胺酸神經系統之N-methyl-D-aspartate (NMDA)受體參與調節壓力反應。焦慮及憂鬱皆屬於壓力反應，長期之壓力及焦慮會導致憂鬱症狀。雖然大鼠的焦慮程度有個體差異，但目前尚未瞭解動物之NMDA受體活性是否與其焦慮程度有關。D-cycloserine(DCS)是 NMDA受體的部分致效劑，近期陸續有文獻證實DCS應用在治療精神疾病之效果。本實驗將探討DCS之藥效強度是否和大鼠之焦慮程度有關。本實驗以雄性Wistar大鼠為材料，將其放入高腳十字迷宮中進行5分鐘之行為試驗，依其停留在開放臂上的時間長短，分別將大鼠區分為低焦慮組及高焦慮組。隔天給予大鼠腹腔注射DCS (5、10或30 mg/kg)或生理食鹽水(1 ml/kg), 30分鐘復再進行一次高腳十字迷宮試驗；6 天後實施一次強迫游泳試驗15分鐘，隔天再注射一次上述劑量之DCS後，再實施一次5分鐘之強迫游泳試驗。實驗結果顯示DCS(30 mg/kg)增加低焦慮組大鼠的焦慮程度，但高焦慮組大鼠的焦慮程度不受DCS影響，且DCS不影響大鼠在強迫游泳試驗中之憂鬱行為。本實驗首次證明DCS之行為藥效和大鼠的焦慮程度有關，顯示精神藥物之藥效具有個體差異。本研究結果推論NMDA受體之甘膠酸結合位之活性可能參與調節大鼠之焦慮行為。

關鍵字

麩胺酸神經系統 ； 個體差異 ； 焦慮 ； 高腳十字迷宮 ； D-cycloserine ； NMDA受體

並列摘要

It has been demonstrated that glutamatergic N-methyl-D-aspartate(NIVIDA) receptor is involved in stress response. Anxiety is the first response to acute stress; chronic anxiety precedes depression. Although the individual differences in rat's anxiety level have been reported, it still remains unknown Iiether the function of NMDA receptor is correlated to anxiety. D-cycloserine (DCS), a partial agonist of glycine binding site of NMDA receptor, has been reported to be a psycho-active agent in some behavioral tasks. Here, we examed whether low and high anxiety rats response differently to DCS. Male Wistar rats ere screened by using elevated plus-maze and were divided into ‘low anxiety' and 'high anxiety' subgroups according to the time spent on the open arm. Thirty minutes after the administration of DCS (5.10, or 30 mg/kg i.p.) or saline, the animals were tested again by plus-maze on the second day. Six days later, rats received a 15-minute forced swim test. Swimming test as repeated for 5 minutes on the following day after the treatment of DCS as what they had received before. Results showed that DCS at dose of 30 mg/kg increased the anxiety level of lo but not high anxiety group. The immobility time in the forced swim test as not affected by DCS either low or high anxiety group. In conclusion, the behavioral effects of DCS depend on the anxiety level, suggesting that the function of glycine binding site on NIVIDA receptor may play a role in regulating anxiety, amid that the responses to psycho-active drugs have individual differences.

並列關鍵字

Glutamatergic system Individual differences ； Anxiety ； Elevated plus-maze ； D-cycloserine ； NMDA receptor