葛根素為中藥葛根活性成分之一，研究證實可增加腦血流量(7)及保護腦缺血造成大鼠腦部之損壞與運動之障礙(8)。因此，本研究以被動迴避學習反應探討葛根素(puerarin)對學習獲得障礙誘發劑scopolamine、necamylamine、p-chloroamphetamine、MK-801及記憶鞏固障礙誘發劑cycloheximide之影響。 葛根素對學習獲得障礙誘發劑之作用，對於乙醯膽鹼毒蕈鹼接受器拮抗劑scopolamine無改善作用，但對乙醯膽鹼尼古丁接受器拮抗劑mecamylamine、sertonin釋放促進劑p-chloroamphetamine及非NMDA接受器拮抗劑MK-801等具明顯改善作用。 葛根素對記憶鞏固障礙誘發劑CXM之改善作用，此改善作用均可被毒蕈鹼接受器拮抗劑SCOP、尼古丁接受器拮抗劑MECA及serotonin釋放促進劑PCA拮抗；進一步，其改善作用可被突觸後5-HT2接受器致效劑DOI、非選擇性突觸後α接受器拮抗劑phenoxybenzamine及非選擇性突觸後β接受器拮抗劑propanolol拮抗，但無法被5-HT1A接受器致效劑8-OH-DPAT所拮抗。 葛根素經腦室給藥後，在5,7-DHT破壞dorsal raphe後，對CXM誘發大鼠記憶鞏固之障礙仍具改善作用，但在6-OHDA破壞locus coeruleus後，只在10 mg劑量下具改善作用(p<0.01)，但仍比假手術組的改善作用明顯下降。另外，葛根素經腦室給藥後，於側腦室給與cholinergic neurotoxin AF64A誘發大鼠學習記憶障礙亦具拮抗作用。 綜合上述結果，顯示葛根素可增強記憶形成過程中的學習獲得及記憶獲得，其作用機轉可能直接作用於中樞cholinergic system或間接經由中樞noradrenergic system、serotonergic system及exitatory amino acid system之調節而影響中樞cholinergic system改變Ach之活性所致；亦與蛋白質之合成有關。; Puerarin (PUR) is one active ingredient of Pueraria lobata (Willd.) Ohwi.. Modern pharmacological studies pointed out puerarin protected brain damage and motor dysfunction induced by cerebral ischemia in rats. On this acount, the present study was intended to investigate the attenuating effect of puerarin on drug (scopolamine, mecamylamine, p-chloroamphetamine and MK-801)-induced learning acquisition impairment and the cycloheximide-induced memory consolidation impairment. PUR administered 30 min before the training trial intraperitoneally attenuated the memory impairment induced by mecamylamine, p-chloroamphetamine, MK-801 and cycloheximide but not scopolamine in the passive avoidance task. The puerarin-induced recovery from the CXM-induced memory impairment was blocked by scopolamine, mecamylamine, p-chloroamphetamine, DOI, propranolol and phenoxybenzamine but not 8-OH-DPAT. Furthermore, PUR administrated intracerebroventricularly attenuated the memory impairment induced by CXM or AF64A, and the CXM-induced memory impairment in 5,7-DHT-induced dorsal raphe lesioned but not 6-OHDA locus coeruleus lessioned rats. From these results, we suggest that the attenuating effects of puerarin on the memory impairment were due to increasing the excitatory amino acid activity and cholinergic activity via the noradrenergic system in locus coeruleus and partially the serotonergic system in dorsal raphe.
