A post-ischaemic single administration of galanthamine, a cholinesterase inhibitor, improves learning ability in rats

Transient forebrain ischaemia is widely observed in clinical practice. We h ave examined the effect of a single administration of the cholinesterase in hibitor galanthamine (2 mg kg(-1), i.p.) 25 min after reperfusion in male S prague-Dawley rats (180 +/- 20 g) after a 20-min common carotid artery occl usion. Twenty-four-hours post-ischaemia there was no difference in motor co-ordina tion or muscle tonus of the rats treated with or without galanthamine as as sessed by the rota-rod test. Learning ability was examined using the shuttl e-box test, evaluating the latency time and the number of errors for six da ys in succession. The performance of the ischaemic saline-injected rats was significantly impaired on days 4, 5, 6 (latency time) compared with the no n-ischaemic rats and with the ischaemic animals administered galanthamine ( P < 0.05). Similar results were obtained when counting the number of errors (failure to cross the cage during conditioned or unconditioned stimulus). The monitoring of body temperature during the first 12-h post-ischaemia did not show any significant difference between the groups. The data showed a beneficial effect of galanthamine on the recovery of lear ning ability when administered once only post-ischaemia. This suggests a di rect effect on the early pathologic mechanisms of CNS damage. Cholinesteras e inhibitors may prove useful in the early clinical treatment of ischaemic conditions.