Lateralized Effects of Intra-amygdalar Losartan Infusion on Anxiety in Rats with a Model of Depression

Abstract

This study investigated the effects of Angiotensin II (Ang II) and losartan, a selective Ang II type 1 receptor (AT1) antagonist when unilaterally infused (left or right) into the central nucleus of the amygdala (CeA) on anxiety-like behaviour in male Wistar rats with a model of depression (bilateral olfactory bulbectomy, OBX). Microinjections of Ang II (0.5 μg/side) into the CeA of OBX rats did not alter anxiety-like behaviour, as assessed in the elevated plus-maze test. In contrast, inhibition of ATI receptors in the left or right CeA by losartan (100 μg/side) induced an anxiolytic-like effect, evidenced by an increased number and time of open-arm entries, a higher open/total entries ratio, a higher open/total time ratio, and a decreased number and time of closed-arm entries. For the first time, our study demonstrates the anxiolytic-like effect of losartan when infused unilaterally into the CeA of OBX rats. Additionally, our findings suggest a differential distribution of AT1 receptors in the left and right CeA. This asymmetric distribution may contribute to the lateralized effects of AT1 receptor antagonist and indicates that AT1 receptor expression levels could play an important role in depression.