Reduced anxiety-like behavior in transgenic rats with chronically overproduction of angiotensin-(1-7): Role of the Mas receptor

Abstract

Angiotensin-(1-7) [Ang-(1-7)], a counterregulatory peptide of the renin-angiotensin system (RAS), exerts its cardiovascular and renal functions through the G-protein-coupled receptor Mas. More recently, Ang-(1-7) has also been implicated in the control of emotional states related to fear and anxiety. Here, we tested the hypothesis that transgenic rats overexpressesing Ang-(1-7) (TGR) show reduced anxiety-like behavior in two distinct animals models, the Elevated Plus Maze (EPM) and Vogel Conflict Test (VCT). Sprague-Dawley rats (SDs) were used as controls. In addition, we also verified whether this phenotype depend on activation of the Mas receptor. In line with our hypothesis, TGR rats showed an increase in the percentage of time and entries in the open arms of the EPM. There was also an increase in the number of punished licks in VCT. These phenotypes were reversed by ICV injection of the Mas receptor antagonist, A779, but not by the AT₂ and MrgD receptor antagonist, PD123319. These results suggest that chronic elevation of Ang-(1-7) levels results in a phenotype characterized by reduced anxiety-like behavior, possibly due to higher activation of the Mas receptor. Therefore, facilitation of the Ang-(1-7)/Mas receptor signaling may be further investigated as an additional strategy for the treatment of anxiety-related disorders.

Keywords: AT(2) receptor; Angiotensin-(1–7); Anxiety; Mas receptor; MrgD receptor; Transgenic rats.