| 摘要: | 本研究探討溫腎壯陽藥蛇床子(Cnidium monnieri(L.)CUSSON)之石油醚萃取層（簡稱CF）及其成分蛇床子素(osthole)對大鼠由scopolamine(SCOP)誘發被動迴避學習暨水迷宮空間學習操作之影響。首先獲得CF口服劑量0.1~0.6 g/kg 均能增強雌、雄性大鼠學習記憶。當其併用週邊乙醯膽鹼拮抗劑 scopolamine methylbromide(M-SCOP), 或週邊交感神經毒素6-hydroxydopamine(6-OHDA), 其增強學習記憶作用不被阻斷。顯示CF之改善學習記憶障礙作用機轉與週邊乙醯膽鹼及catecholamine神經系統無關。但當雄性大鼠切除腎上腺後，CF之改善學習障礙作用被阻斷，顯示，CF之改善學習障礙作用與腎上腺系統有關。 另本研究進一步探討CF及蛇床子素於雌性大鼠卵巢切除後對於空間學習操作之影響。結果發現給予scopolamine之雌性大鼠血中estradiol的濃度低於正常鼠，而口服CF(0.3, 0.6 g/kg)之雌性大鼠可使血中estradiol之濃度恢復與正常鼠相當。同時發現對於卵巢切除後在空間學習操作之障礙，蛇床子素皮下注射(3, 10 mg/kg)有明顯改善學習障礙，且對記憶再現有改善；另蛇床子素經腦室給藥(10, 30 ?g/brain)可改善再學習過程。綜合上述之結果，蛇床子素不論皮下或腦部給藥均具改善雌性大鼠卵巢切除後水迷宮空間操作能力障礙之作用，其作用機轉可能與提升estradiol 有關。 再者本研究更進一步探討蛇床子素增強學習記憶與中樞神經系統之關 係。當其併用中樞乙醯膽鹼神經毒素ethylcholine aziridinium (AF64A 3 ?g/brain)、中樞血清素神經毒素5,7-dihydroxytryptamine (5,7-DHT 25 ?g/brain)、中樞腎上腺素β拮抗劑propranolol(80 ng/brain) 及中樞腎上腺素α2拮抗劑yohimbine(80 ng/brain)誘發水迷宮空間學習操作障礙不具改善作用。顯示蛇床子素改善學習障礙作用與中樞乙醯膽鹼神經系統、血清素神經系統、腎上腺素β接受器及腎上腺素α2接受器無關。但當併用中樞catecholamine神經毒素6-hydroxydopamine (6-OHDA 25 ?g/brain)、中樞腎上腺素α1拮抗劑phenoxybenzamine(80 ng/brain)誘發空間學習操作障礙，蛇床子素(10 ?g/brain, i.c.v)均明顯的改善作用。顯示蛇床子素，改善學習障礙作用與中樞catecholamine神經系統及腎上腺素α1接受器有關。; The present study was designed to investigate the effects of petroleum ether fraction of Cnidii Fructus (Abbreviate CF) and its principle constituent osthole on the scopolamine-induced performance impairment of inhibitory avoidance task and Morris water maze in rats. Firstly, CF(0.1~0.6 g/kg p.o.) ameliorated the scopolamine-induced performance impairment on inhibitory avoidance learning and water maze in both male and female rats. Furthermore, scopolamine methylbromide and 6-hydroxydopamine did not block the ameliorating effects of CF on scopolamine-induced performance impairment in rats. It showed that the ameliorating performance impairment of CF is not associated with peripheral catecholamine neuron system. However, adrenalectomy blocked the ameliorating effects of CF on scopolamine-induced performance impairment in male rats. It showed that the ameliorating performance impairment of CF was associated with adrenal gland. Secondly, we further investigated the effects of CF and osthole on the spatial performance in scopolamine-treated or ovariectomized female rats. The result showed that the plasma estradiol levels of scopolamine-treated female rats were lower than those of normal ones. Moreover, CF at the oral dose of the 0.3-0.6 g/kg reversed the lower plasma estradiol levels caused by scopolamine in female rats. In the spatial performance deficit of ovariectomized rats, osthole (3 and 10 mg/kg, sc) significantly improved the spatial performance deficit and memory retrieval. Furthermore, osthole (3 and 10 ?g/brain) improved the spatial performance deficit. According to the above results, osthole ameliorated the performance impairment induced by ovariectomy on water maze in female rats no matter administrated in subcutaneous or brain infusion. The mechanism was probably associated with improvement of the plasma estradiol levels. Finally, we investigated the relationship between the ameliorating the learning memory of osthole and central neuronal system. The results showed that osthole at the dose of the 10μg/brain (i.c.v.)did not ameliorate the performance impairment induced by ethylcholine aziridinium(AF64A 3 ?g/brain), 5,7-dihydroxytryptamine (5,7-DHT 25 ?g/brain), propranolol (80 ng/brain) and yohimbine (80 ng/brain) on Morris water maze. These results suggested that ameliorating performance impairment of osthole is not associated with central cholinergic neuronal system, serotonergic neuronal system, adrenergic ? receptor and adrenergic ?2 receptor. However, osthole at the dose of the 10μg/brain (i.c.v.) significantly improved the deficit of spatial performance induced by 6-hydroxydopamine (6-OHDA 25 ?g/brain) and phenoxybenzamine (80μg/brain). It suggested that ameliorating performance impairment of osthole was associated with central cate |
