Hydergine enhances memory in mice.

Moderate improvement of cognitive function has been reported in many clinical studies of Hydergine (HYD) but in only a few controlled dose-response studies in animals. We therefore evaluated the effects of HYD upon one-week retention of training by T-maze active avoidance and by one-trial passive avoidance in a stepthrough apparatus. HYD satisfied seven criteria for a memory enhancing drug, as follows. Post-training subcutaneous injection improved memory recall scores; the dose-response curve was the inverted-U typical of many memory enhancers. Post-training intracerebral injection showed a similar effect, indicating a central mechanism of action. Pre-testing subcutaneous injection had a similar effect, indicating enhancement of retrieval processes. Pre-training subcutaneous injection had a similar effect, at much lower doses than post-training injection. HYD did not improve acquisition of T-maze active avoidance, indicating that its effects were on memory processing rather than learning per se. Enhancement by post-training injection declined as the training-to-injection interval increased; this temporal gradient is typical of memory-enhancing drugs. Subcutaneous HYD reversed the amnestic effects of anisomycin (a protein synthesis inhibitor) and of scopolamine (an anticholinergic drug). The results characterize HYD as an effective enhancer of memory processing and of memory retrieval, in the mouse paradigms of active avoidance and passive avoidance.