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 II (AII) 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 AII 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, AII, but not angiotensin IV or angiotensin1–7 induced a dose-dependent and reversible amnesia without altering locomotor activity, exploratory behavior or anxiety state. The effect of AII was blocked in a dose-dependent manner by the AII-type 2 receptor (AT2) antagonist PD123319 but not by the AII-type 1 receptor (AT1) antagonist losartan. By themselves, neither PD123319 nor losartan had any effect on memory expression. Our data indicate that intra-CA1 AII hinders retrieval of avoidance memory through a process that involves activation of AT2 receptors.