Improvement of impaired memory in mice by huperzine A and huperzine B

Both huperzine A (Hup-A) and huperzine B(Hup-B) are new alkaloids isolated from Huperzia serrata (Thunb Trev). It has been shown in this laboratory that Hup-A and Hup-B are selective AChE inhibitors which exhibit larger therapeutic indices than does physostigmine (Phy). Using a step-down method, the effects of Hup-A and Hup-B on various forms of experimentally-produced impaired memory function in mice were examined. Mice received a single training trial on a passive avoidance task followed by a retention trial 24h later. Immediately after training, each adult mouse received one of the following amnestic treatments: maximal electroconvulsive shock (MES), or an injection of scopolamine (Scop), NaNO2 or cycloheximide (CXM). Step-down latency (SDL) and escape latency (EL) were measured and used as parameters of memory performance. In control mice. each amnestic treatment produced retrograde amnesia. However, Hup-A or Hup-B administered immediately after each of the amnestic treatments significantly reversed the MES, Scop, NaNO2- or CXM-induced disruptions of memory retention for passive avoidance tasks. Hup-A or Hup-B also markedly improved the retention of the learned task 24h later in aged mice. These improvements or normalization of impaired memory function were observed at doses of 1OO-150 yg/kg ip and 140-160 yg/kg ig (Hup-A) or of l.0-1.5 mg/kg ip and 2.4 mg/kg ig (Hup-B). Phy (0.125-0.175 mg/kg ip) for comparison, were active in all of the various experimental types of amnesia and had about 10 times the potency of Hup-B, but less than that of Hup-A.