Anxiolytic effect of alamandine in male transgenic rats with low brain angiotensinogen is dependent on activation of MrgD receptors

Laura Amado Costa; Laura B Oliveira Amaral; Flávio A G Mourão; Michael Bader; Robson A S Santos; Maria José Campagnole-Santos; Lucas M Kangussu

doi:10.1016/j.yhbeh.2024.105551

Anxiolytic effect of alamandine in male transgenic rats with low brain angiotensinogen is dependent on activation of MrgD receptors

Horm Behav. 2024 Apr 27:163:105551. doi: 10.1016/j.yhbeh.2024.105551. Online ahead of print.

Authors

Laura Amado Costa¹, Laura B Oliveira Amaral¹, Flávio A G Mourão², Michael Bader³, Robson A S Santos⁴, Maria José Campagnole-Santos⁴, Lucas M Kangussu⁵

Affiliations

¹ Department of Morphology, Biological Sciences Institute, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil.
² Department of Physiology and Biophysics, Biological Sciences Institute, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil.
³ National Institute of Science and Technology in Nanobiopharmaceutics (INCT-Nanobiofar); Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany; Institute for Biology, University of Lübeck, Lübeck, Germany; Charité University Medicine Berlin, Berlin, Germany; German Center for Cardiovascular Research (DZHK), Partner Site Berlin, Germany.
⁴ Department of Physiology and Biophysics, Biological Sciences Institute, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil; National Institute of Science and Technology in Nanobiopharmaceutics (INCT-Nanobiofar).
⁵ Department of Morphology, Biological Sciences Institute, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil; National Institute of Science and Technology in Nanobiopharmaceutics (INCT-Nanobiofar). Electronic address: lucaskangussu@ufmg.br.

PMID: 38678724
DOI: 10.1016/j.yhbeh.2024.105551

Abstract

Alamandine is a peptide hormone belonging to the renin-angiotensin system (RAS). It acts through the Mas-related G-protein coupled receptor type D, MrgD, which is expressed in different tissues, including the brain. In the present study, we hypothesize that a lack of alamandine, through MrgD, could cause the anxiety-like behavior in transgenic rats with low brain angiotensinogen [TGR(ASrAOGEN)680]. Adult male transgenic rats exhibited a significant increase in the latency to feeding time in the novelty suppressed feeding test and a decrease in the percentage of time and entries in the open arms in the elevated plus maze. These effects were reversed by intracerebroventricular infusion of alamandine. Pretreatment with D-Pro⁷-Ang-(1-7), a Mas and MrgD receptor antagonist, prevented the anxiolytic effects induced by this peptide. However, its effects were not altered by the selective Mas receptor antagonist, A779. In conclusion, our data indicates that alamandine, through MrgD, attenuates anxiety-like behavior in male TGR(ASrAOGEN)680, which reinforces the importance of the counter-regulatory RAS axis as promising target for the treatment of neuropsychiatric disorders.

Keywords: Alamandine; Anxiety; MrgD receptor; TGR(ASrAOGEN)680; Transgenic rats with low brain angiotensinogen.