ATTENUATION OF SCOPOLAMINE-INDUCED SPATIAL-LEARNING IMPAIRMENTS BY ANANGIOTENSIN-IV ANALOG

Recently, a receptor for the angiotensin II(3-8) (Ang IV) hexapeptide, was discovered in the hippocampus, suggesting a possible role in lear ning. The present study utilized intracerebroventricularly (icv) infus ed scopolamine hydrobromide (scop) to disrupt spatial learning in the circular water maze, followed by the Ang IV analog norleucine(1)-Ang I V (Nle(1)-Ang IV), to restore normal performance. Rats were icy pretre ated with either scop or artificial cerebrospinal fluid (aCSF) followe d by either icy injected Nle(1)-Ang IV or aCSF, and then behaviourally tested. During acquisition training, each animal's latency to locate the platform, path distance, speed, and efficiency ratios were measure d. A probe trial was conducted on the final day of training and the ti me spent in the target quadrant and the number of crossings over the f ormer location of the platform (annulus crossings) were observed. The results indicate that those animals treated with scop followed by aCSF performed poorly during acquisition training as compared with control s. In contrast, those animals that received scop followed by Nle(1)-An g IV attained equivalent latencies, distances, and efficiency ratios t o find the platform as those achieved by controls. There were no obser ved differences in swimming speed, thus arguing against drug-induced m otor impairment. During the probe trial, animals treated with scop fol lowed by aCSF spent less time in the target quadrant and made fewer an nulus crossings as compared to controls, while the scop, Nle(1)-Ang IV treated animals performed equivalently to controls. These results sug gest that Nle(1)-Ang IV acts to counteract the disruption of spatial l earning induced by scopolamine. (C) 1998 Elsevier Science B.V.