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 (2 mgkg−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.