EFFECTS OF INDELOXAZINE HYDROCHLORIDE, A CEREBRAL ACTIVATOR, ON PASSIVE-AVOIDANCE LEARNING IMPAIRED BY DISRUPTION OF CHOLINERGIC TRANSMISSION IN RATS

The effect of indeloxazine [(+/-)-2-[(inden-7-yloxy)methyl]morpholine hydrochloride, YM-08054], a cerebral activator, on passive avoidance l earning by disruption of cholinergic transmission was investigated in rats. Indeloxazine prolonged the latency for stepping out of an illumi nated compartment into a dark compartment, in both mature and aged rat s. Disruption of cholinergic transmission was induced by injection of scopolamine, ethylcholine, treatment with aridinium ion (AF64A) and by lesioning the nucleus basalis magnocellularis. The shortened latency in these models was prolonged when indeloxazine was administered befor e training in doses which did not affect spontaneous movement or the r esponse to pain in mature rats and administration of indeloxazine, imm ediately after training, also had an ameliorating effect on passive av oidance in the lesioned rats. In biochemical studies, indeloxazine inc reased the extracellular concentration of acetylcholine in the frontal cortex of mature rats. These results suggest that indeloxazine posses ses facilitatory effects on cerebral function, in part due to activati on of the central cholinergic system.