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 have examined the effect of a single administration of the cholinesterase inhibitor galanthamine (2mg kg(-1) i.p.) 25 min after reperfusion in male Sprague-Dawley rats (180 +/- 20 g) after a 20-min common carotid artery occlusion. Twenty-four-hours post-ischaemia there was no difference in motor co-ordination or muscle tonus of the rats treated with or without galanthamine as assessed by the rota-rod test. Learning ability was examined using the shuttle-box test, evaluating the latency time and the number of errors for six days in succession. The performance of the ischaemic saline-injected rats was significantly impaired on days 4, 5, 6 (latency time) compared with the non-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 learning ability when administered once only post-ischaemia. This suggests a direct effect on the early pathologic mechanisms of CNS damage. Cholinesterase inhibitors may prove useful in the early clinical treatment of ischaemic conditions.