Comparative studies of huperzine A, donepezil, and rivastigmine on brain acetylcholine, dopamine, norepinephrine, and 5-hydroxytryptamine levels in freely-moving rats
Comparative studies of huperzine A, donepezil, and rivastigmine on brain acetylcholine, dopamine, norepinephrine, and 5-hydroxytryptamine levels in freely-moving rats
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DOI：
10.1111/j.1745-7254.2006.00411.x
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发表时间：
2006-09-01
影响因子：
8.2
通讯作者：
Tang, Xi-can
中科院分区：
文献类型：
--
作者：
Liang, Yan-qi;Tang, Xi-can
目的：探讨胆碱酯酶抑制剂石杉碱甲、多奈哌齐和卡巴拉汀对自由活动大鼠皮层和海马神经递质的影响。方法：采用双探针脑微透析技术和高效液相色谱电化学检测法检测神经递质。结果如下：我们的研究结果表明，石杉碱甲（0.25，0.5和0.75 μ mol/kg，po）剂量依赖性地提高细胞外乙酰胆碱（ACh）在内侧前额叶皮层（mPFC）和海马的水平。多奈哌齐（5.4 μ mol/kg）或卡巴拉汀（1 μ mol/kg）经口给药也引起MPFC和海马中ACh的显著增加。皮质乙酰胆碱酯酶（AChE）抑制的时间过程与3个抑制剂反映了在相同剂量的ACh的增加。口服石杉碱甲（0.5 μ mol/kg）和多奈哌齐（5.4 μ mol/kg）后ACh的显著升高与mPFC或海马中多巴胺（DA）释放的显著增加有关。3种抑制剂均不影响mPFC和海马中的去甲肾上腺素（NE）和5-羟色胺（5-HT）水平。石杉碱甲和卡巴拉汀的作用不依赖于给药途径，但多奈哌齐口服途径的有效性低于ip注射。石杉碱甲以0.5pmol/kg的剂量每日一次连续口服30天后，其升高ACh水平的能力没有改变。结论：目前的研究结果表明，以摩尔计，石杉碱甲在增加mPFC ACh和DA水平方面的效力分别与11倍和2倍剂量的多奈哌齐和卡巴拉汀相似，并且口服给药后具有更长的持续作用。
Aim: To assess the effects of cholinesterase inhibitors huperzine A, donepezil and rivastigmine on cerebral neurotransmitters in the cortex and hippocampus in freely-moving rats. Methods: Double-probe cerebral microdialysis and HPLC with electrochemical detection were used to detect neurotransmitters. Results: Our results showed that huperzine A (0.25, 0.5, and 0.75 mu mol/kg, po) dose-dependently elevated extracellular acetylcholine (ACh) levels in the medial prefrontal cortex (mPFC) and hippocampus. Oral administration of donepezil (5.4 mu mol/kg) or rivastigmine (1 mu mol/kg) also elicited significant increases in ACh in the MPFC and hippocampus. The time course of cortical acetylcholinesterase (AChE) inhibition with the 3 inhibitors mirrored the increases of ACh at the same dose. The marked elevation of ACh after oral administration of huperzine A (0.5 mu mol/kg) and donepezil (5.4 mu mol/kg) was associated with a significantly increased release of dopamine (DA) in the mPFC or hippocampus. None of the 3 inhibitors affected norepinephrine (NE) and 5-hydroxytryptamine (5-HT) levels in the mPFC and hippocampus. The effects of huperzine A and rivastigmine did not depend on the route of administration, but donepezil was less efficacious by the oral route than by ip injection. The ability of huperzine A to increase ACh levels was unchanged when tests were performed after multiple oral administration of the drug at 0.5 pmol/kg, once per day for 30 d. Conclusion: The present findings showed that, in molar terms, huperzine A had similar potency on increasing mPFC ACh and DA levels as compared to the 11- and 2-fold dosages of donepezil and rivastigmine, respectively, and had longer lasting effects after oral dosing.