Attenuation of scopolamine-induced spatial learning impairments by an angiotensin IV analog

Recently, a receptor for the angiotensin II(3-8) (Ang IV) hexapeptide, was discovered in the hippocampus, suggesting a possible role in learning. The present study utilized intracerebroventricularly (icv) infused scopolamine hydrobromide (scop) to disrupt spatial learning in the circular water maze, followed by the Ang IV analog norleucine(1)-Ang IV (Nle(1)-Ang IV), to restore normal performance. Rats were icy pretreated with either scop or artificial cerebrospinal fluid (aCSF) followed 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 measured. A probe trial was conducted on the final day of training and the time spent in the target quadrant and the number of crossings over the former 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 controls. In contrast, those animals that received scop followed by Nle(1)-Ang IV attained equivalent latencies, distances, and efficiency ratios to find the platform as those achieved by controls. There were no observed differences in swimming speed, thus arguing against drug-induced motor impairment. During the probe trial, animals treated with scop followed by aCSF spent less time in the target quadrant and made fewer annulus crossings as compared to controls, while the scop, Nle(1)-Ang IV treated animals performed equivalently to controls. These results suggest that Nle(1)-Ang IV acts to counteract the disruption of spatial learning induced by scopolamine. (C) 1998 Elsevier Science B.V.