FACILITATORY EFFECTS OF HUPERZINE A AND B ON LEARNING AND MEMORY OF SPATIAL DISCRIMINATION IN MICE

Both huperzine A (Hup-A) and B (Hup-B)are new alkaloids isolated from the Chinese herb Huperzia serrata. It has been demonstrated in our laboratory that these two alkaloids exhibited more selective inhibitory activity on AChE than physostigmine (Phys) (2). By using Y maze method, the facilitatory effect on learning and memory of spatial discrimination task in mice was studied. Mice were placed on an electrified grid in a Y maze and learned to run to a safe area which was the counter arm defined according to the mice run directly into the arm during the first electric shock. The criterion of learning, memory retention and memory retrieval was met when the mice had chosen the safe area in 10 consecutive trials.Hup-A (0.075 mg/kg) and Hup-B (0.5 mg/kg) injected intraperitoneally before training caused significant decrease in the number of trials. Administration of Hup-A (0. 075～0.125 mg/kg) or Hup-B (0.6～0.8 mg/kg) 10 min before hypercapnia significantly prevented the CO₂-induced impairment of acquisition. These facilitatory effects on acquisition were also seen after oral Hup-A doses of 0.1 mg/kg and Hup-B doses of 0.8 mg/kg. Hup-A (0.075～0.15 mg/kg ip) or Hup-B (0.4～1.2 mg/kg ip) facilitated memory retention and retrieval when administrated immediately after training or 6 h and 12 h after training. Generally, the dose-response curves were bell-shaped. When Phys was used for comparison, it was active in all the above mentoned experiments and was less potent than Hup-A, but about 3～5 times more potent than Hup-B. Based on the present results, it is suggested that Hup-A and Hup-B should be of therapeutic value in humans for improving cognitive functions impaired by various noxious influences. Initial clinical studies on Hup-A has revealed various degrees of positive results shown by improvement in memory.