Lateralized Active Avoidance Learning and Memory to Ang II and Losartan Microinjected into Amygdala in Rats Depression Model

Abstract

Depression is a widespread socially significant disease. Studies aiming to reveal the pathogenesis of depression have lasted for decades, but the specific mechanisms remain unclear. Olfactory bulbectomy (OBX) in rats provides a well-validated animal model of depression and Alzheimer's disease. The aim is to evaluate the involvement of Ang II and AT1 receptors in learning and memory after unilateral infusion of Ang II and losartan (specific AT1 antagonist) into CeA (central nucleus of the amygdala) in rats with a model of depression (bilateral olfactory bulbectomy, OBX). The effects of Ang II and losartan infused into CeA on the avoidance performance in OBX rats using the active avoidance (shuttle box) test were investigated. A stereotaxic technique was used for bilateral implantation of guide cannulae into CeA. Fourteen days after OBX, Ang II, or losartan were microinjected unilaterally into CeA of rats with depressive-like behaviour. For the first time it was found that Ang II infused into the left CeA impaired learning and memory, while losartan infused into the left CeA significantly improved these processes and prevented the memory deficits induced by the bulbectomy. The data suggest an involvement of amygdala Ang II and AT1 receptors in learning and memory of rats and a differential distribution of the AT1 receptors in the left and right central nucleus of the amygdala in rats with a model of depression.