ORIGINAL RESEARCH article
Front. Endocrinol.
Sec. Experimental Endocrinology
Volume 16 - 2025 | doi: 10.3389/fendo.2025.1650458
This article is part of the Research TopicFunction of hormones, their receptors and binding proteinsView all 9 articles
Crhr1 and epinephrine utilize the central Ras-MAPK pathway in mediating the acute stress-related locomotor activity in zebrafish larvae
Provisionally accepted
Enezi Khalid1
Mathilakath Vijayan2*- 1University of Calgary, Calgary, Canada
- 2Biology, University of Calgary, Calgary, ON, Canada
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Although the Crh-Crhr1 system is the proximal trigger for the stressor-induced corticosteroid release, its role in initiating the fight-or-flight response to an acute stressor is unclear. We hypothesized that the Crh-Crhr1 system deploys the central Ras-Mapk (mitogen-activated protein kinase) pathway and rapidly increases locomotor activity in zebrafish larvae. We tested this using an acute stressor-induced hyperactivity model in larval zebrafish that is Crhr1-dependent. The larval hyperactivity response to stress disappeared after pretreatment with BAY-293 (a Ras inhibitor). Acute CRH exposure stimulated hyperactivity but at a lower magnitude than epinephrine; however, both responses were inhibited by BAY-293. Immunohistochemical localization revealed rapid phosphorylation of ERK1/2 in the pallium and hypothalamic regions after acute CRH and epinephrine treatment. The lack of Crhr1 (crhr1-/-) upregulated the α1-adrenoceptors (adra1ab and adra1ba) and abolished the epinephrine-induced, but not the forskolin-induced hyperactivity. The acute stressor also increased the transcript abundance of c-fos, a commonly used marker of neuronal activation and plasticity. This immediate early gene response to stress was mimicked by epinephrine, but not by Crh treatment, and was Ras-dependent. The acute stressor- or epinephrine-induced c-fos response was unaltered in larvae lacking a functional Crhr1. This study reveals the activation of the Ras-Mapk pathway by Crhr1 as a central mechanism modulating acute stress-induced larval hyper locomotor activity but not the c-fos response in zebrafish. Altogether, our results suggest a complementary but essential role for Crhr1 in facilitating the epinephrine-mediated fight-or-flight response but not the stress-habituation response.
Keywords: cortisol, stress response, behaviour, HPI, CRH, Epinephrine, c-Fos Disclosure summary: The authors have nothing to declare
Received: 19 Jun 2025; Accepted: 15 Aug 2025.
Copyright: © 2025 Khalid and Vijayan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Mathilakath Vijayan, Biology, University of Calgary, Calgary, N2L 3G1, ON, Canada
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.