Accepted Article This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/jne.12530 This article is protected by copyright. All rights reserved. DR ANDRE S MECAWI (Orcid ID : 0000-0003-4517-6221) Article type : Original Article Sodium appetite elicited by low-sodium diet is dependent on p44/42 MAPK (ERK1/2) activation in the brain Lívia Rocha Natalino Monteiro 1 , Paula Beatriz Marangon 2 , Lucila Leico Kagohara Elias 2 , Luís Carlos Reis 1 , José Antunes-Rodrigues 2 , André Souza Mecawi 1 . 1- Department of Physiological Sciences, Institute of Biological and Health Sciences, Federal Rural University of Rio de Janeiro, Brazil 2- Department of Physiology, Faculty of Medicine of Ribeirao Preto, University of São Paulo, Brazil Correspondence to: Dr. André Souza Mecawi Department of Physiological Sciences, Institute of Biological and Health Sciences, Federal Rural University of Rio de Janeiro, BR465, Km7, Zip Code: 23897-970, Seropedica, RJ, Brazil (e-mail: mecawi.as@gmail.com). Abstract The sodium appetite is regulated by several signalling molecules, among which angiotensin II (ANG II) serves as a key driver of robust salt intake by binding to ANG II type 1 receptors (AT1R) in several regions in the brain. The activation of these receptors recruits the mitogen- activated protein kinase (MAPK) pathway, which has previously been linked to ANG II- induced increases in sodium appetite. Thus, we addressed the involvement of MAPK signalling in the induction of sodium appetite after four days of low-sodium diet consumption. An increase in extracellular signal-regulated kinase (ERK) phosphorylation in the laminae terminalis and mediobasal hypothalamus was observed after low-sodium diet consumption. This response was reduced by intracerebroventricular (icv) microinjection of an AT1R antagonist into the laminae terminalis but not the hypothalamus. This result indicates that low-sodium diet consumption activates the MAPK pathway via ANG II/AT1R signalling on the laminae terminalis. On the other hand, activation of the MAPK pathway in the mediobasal hypothalamus after low-sodium diet consumption seems to involve another