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Aim:To assess the effects of cholinesterase inhibitors huperzine A,donepeziland rivastigmine on cerebral neurotransmitters in the cortex and hippocampus infreely-moving rats.Methods:Double-probe cerebral microdialysis and HPLC withelectrochemical detection were used to detect neurotransmitters.Results:Ourresults showed that huperzine A(0.25.0.5,and 0.75μmol/kg,po)dose-depen-dently elevated extracellular acetylcholine(ACh)levels in the medial prefrontalcortex(mPFC)and hippocampus.Oral administration of donepezil(5.4μmol/kg)orrivastigmine(1μmol/kg)also elicited significant increases in ACh in the mPFC andhippocampus.The time course of cortical acetylcholinesterase(ACHE)inhibitionwith the 3 inhibitors minored the increases of ACh at the same dose.The markedelevation of ACh after oral administration of huperzine A(0.5μmol/kg)anddonepezil(5.4μmol/kg)was associated with a significantly increased release ofdopamine(DA)in the mPFC or hippocampus.None of the 3 inhibitors affectednorepinephrine(NE)and 5-hydroxytryptamine(5-HT)levels in the mPFC andhippocampus.The effects of huperzine A and rivastigmine did not depend on theroute of administration,but donepezil was less efficacious by the oral route thanby ip injection.The ability of huperzine A to increase ACh levels was unchangedwhen tests were performed after multiple oral administration of the drug at 0.5μmol/kg,once per day for 30 d.Conclusion:The present findings showed that,inmolar terms,huperzine A had similar potency on increasing mPFC ACh and DAlevels as compared to the 11-and 2-fold dosages of donepezil and rivastigmine,respectively,and had longer lasting effects after oral dosing.
Aim: To assess the effects of cholinesterase inhibitors huperzine A, donepeziland rivastigmine on cerebral neurotransmitters in the cortex and hippocampus infreely-moving rats. Methods: Double-probe cerebral microdialysis and HPLC withelectrochemical detection were used to detect neurotransmitters. Results: Ourresults showed that huperzine (0.25 μmol / kg po) dose-dependent-dently elevated extracellular acetylcholine (ACh) levels in the medial prefrontalcortex (mPFC) and hippocampus. Oral administration of donepezil (5.4 μmol / kg) orrivastigmine (1 μmol / kg) also elicited significant increases in ACh in the mPFC and hippocampus. The time course of cortical acetylcholinesterase (ACHE) inhibition with the 3 inhibitors minored the increases of ACh at the same dose. The markedelevation of ACh after oral administration of huperzine A (0.5 μmol / kg) anddonepezil (5.4 μmol / kg) was associated with a significantly increased release of doopamine (DA) in the mPFC or hippocampus. None of the 3 inhibitors affected norepinephosphate rine (NE) and 5-hydroxytryptamine (5-HT) levels in the mPFC and hippocampus.The effects of huperzine A and rivastigmine did not depend on theroute of administration, but donepezil was less efficacious by the oral route thanby ip injection. ability of huperzine A to increase ACh levels were unchanged when tests were performed after multiple oral administration of the drug at 0.5 μmol / kg, once per day for 30 d. Conlusion: The present findings showed that, inmolar terms, huperzine A had similar potency on increasing mPFC ACh and DAlevels as compared to the 11-and 2-fold dosages of donepezil and rivastigmine, respectively, and had longer lasting effects after oral dosing.