Effects of huperzine A on learning and retrieval process of discrimination performance in rats
Abstract
Huperzine A (Hup), a new alkaloid isolated from Huperzia serrata (Thunb.) Trev., has powerful and reversible anticholinesterase activity.
Rats were placed on an electrified grid in a Y-maze and learned to run into the light arm (safte area). The criterion of learning or retrieval was met after they had chosen the light arm 10 trials in succession. Hup injected intraperitoneally with100, 167 microg/kg 20 min before training caused a significant decrease in the number of trials to criterion. Facilitation of retrieval was also produced dose-dependently at doses of 36-167 microg/kg ip. Scopolamine 0.2 mg/kg sc, atropine 5 mg/kg sc or hemicholinium 20 microg/10 microL icv antagonized the positive effects of Hup 0.1 mg/kg on retrieval process, but methyl-atropine (2 mg/kg sc) did not. Under the same conditions, physostigmine at doses of 80-180 microg/kg ip improved learning and retrieval process, but quaternary cholinesterase inhibitor neostigmine (30 microg/kg, ip) did not.
Our results suggested that the facilitation actions of Hup were due to an effect on the central cholinergic system, especially the muscarinic system, since M-receptor blockers reversed the actions of Hup, but their quaternary nitrogen derivative methyl-atropine, which did not pass the blood-brain barrier, was inactive.
Besides, the preliminary clinical studies showed that Hup, the first nootropic compound in China, did improve shorter and long-term memory in patients of cerebral arteriosclerosis with memory impairment.
Keywords:
Rats were placed on an electrified grid in a Y-maze and learned to run into the light arm (safte area). The criterion of learning or retrieval was met after they had chosen the light arm 10 trials in succession. Hup injected intraperitoneally with100, 167 microg/kg 20 min before training caused a significant decrease in the number of trials to criterion. Facilitation of retrieval was also produced dose-dependently at doses of 36-167 microg/kg ip. Scopolamine 0.2 mg/kg sc, atropine 5 mg/kg sc or hemicholinium 20 microg/10 microL icv antagonized the positive effects of Hup 0.1 mg/kg on retrieval process, but methyl-atropine (2 mg/kg sc) did not. Under the same conditions, physostigmine at doses of 80-180 microg/kg ip improved learning and retrieval process, but quaternary cholinesterase inhibitor neostigmine (30 microg/kg, ip) did not.
Our results suggested that the facilitation actions of Hup were due to an effect on the central cholinergic system, especially the muscarinic system, since M-receptor blockers reversed the actions of Hup, but their quaternary nitrogen derivative methyl-atropine, which did not pass the blood-brain barrier, was inactive.
Besides, the preliminary clinical studies showed that Hup, the first nootropic compound in China, did improve shorter and long-term memory in patients of cerebral arteriosclerosis with memory impairment.