Angiotensin II disrupts inhibitory avoidance memory retrieval

The brain renin-angiotensin system (RAS) is involved in learning and memory, but the actual role of angiotensin 11 (All) and its metabolites in this process has been difficult to comprehend. This has been so mainly due to procedural issues, especially the use of multi-trial learning paradigms and the utilization of pre-training intracerebroventricular infusion of RAS-acting compounds. Here, we specifically analyzed the action of All in aversive memory retrieval using a hippocampal-dependent, one-trial, step-down inhibitory avoidance task (IA) in combination with stereotaxically localized intrahippocampal infusion of drugs. Rats bilaterally implanted with infusion cannulae aimed to the CA1 region of the dorsal hippocampus were trained in IA, and tested,for memory retention 24 h later. We found that when given into CA1 15 min before IA memory retention test, All, but not angiotensin IV or angiotensin(1-7) induced a dose-dependent and reversible amnesia without altering locomotor activity, exploratory behavior or anxiety state. The effect of All was blocked in a dose-dependent manner by the All-type 2 receptor (AT(2)) antagonist PD123319 but not by the A(II)-type I receptor (AT(2)) antagonist losartan. By themselves, neither PD123319 nor losartan had any effect on memory expression. Our data indicate that intra-CA1 All hinders retrieval of avoidance memory through a process that involves activation of AT(2) receptors. (c) 2006 Elsevier Inc. All rights reserved.