{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T21:49:49Z","timestamp":1782424189774,"version":"3.54.5"},"reference-count":104,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T00:00:00Z","timestamp":1757548800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>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 the locomotor activity in zebrafish larvae.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We tested this using an acute stressor-induced hyperactivity model in larval zebrafish that is Crhr1-dependent, and a pharmacological inhibitor of Ras (BAY-293). <\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The larval hyperactivity response to stress disappeared after pretreatment with BAY-293. Acute CRH exposure stimulated the 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 (<jats:italic>crhr1-\/-<\/jats:italic>) upregulated the a1-adrenoceptors (<jats:italic>adra1ab<\/jats:italic> and <jats:italic>adra1ba<\/jats:italic>) and abolished the epinephrine-induced, but not the forskolin-induced hyperactivity. The acute stressor also increased the transcript abundance of <jats:italic>c-fos<\/jats:italic>, commonly used as a marker of neuronal activation and plasticity. This immediate early gene response to stress was mimicked by epinephrine, but not Crh treatment, and was Ras-dependent. The acute stressor- or epinephrine-induced <jats:italic>c-fos<\/jats:italic> response was unaltered in larvae lacking a functional Crhr1.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>This study reveals the activation of the Ras-Mapk pathway by Crhr1 as a central mechanism modulating the 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.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2025.1650458","type":"journal-article","created":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T04:13:42Z","timestamp":1757564022000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Crhr1 and epinephrine utilize the central Ras-MAPK pathway in mediating the acute stress-related locomotor activity in zebrafish larvae"],"prefix":"10.3389","volume":"16","author":[{"given":"Enezi","family":"Khalid","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathilakath M.","family":"Vijayan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,9,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3999(02)00429-4","article-title":"Hypothalamic\u2013pituitary\u2013adrenal axis, neuroendocrine factors and stress","volume":"53","author":"Tsigos","year":"2002","journal-title":"J Psychosom Res"},{"key":"B2","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1152\/PHYSREV.1997.77.3.591","article-title":"The stress response in fish","volume":"77","author":"Wendelaar Bonga","year":"1997","journal-title":"Physiol Rev"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/B978-0-12-802728-8.00001-1","article-title":"The concept of stress in fish","volume":"35","author":"Schreck","year":"2016","journal-title":"Fish Physiol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/S0044-8486(99)00092-7","article-title":"The acute humoral adrenergic stress response in fish: facts and fiction","volume":"177","author":"Perry","year":"1999","journal-title":"Aquaculture"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1002\/cne.21496","article-title":"Distribution of corticotropin-releasing hormone in the developing zebrafish brain","volume":"505","author":"Chandrasekar","year":"2007","journal-title":"J Comp Neurology"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3389\/FNANA.2015.00002\/BIBTEX","article-title":"Coexpression analysis of nine neuropeptides in the neurosecretory preoptic area of larval zebrafish","volume":"9","author":"Herget","year":"2015","journal-title":"Front Neuroanat"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.coemr.2022.100383","article-title":"Zebrafish as a model to investigate the CRH axis and interactions with DISC1","volume":"26","author":"Eachus","year":"2022","journal-title":"Curr Opin Endocr Metab Res"},{"key":"B8","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1159\/000514778","article-title":"Coordinated action of corticotropin-releasing hormone and cortisol shapes the acute stress-induced behavioral response in zebrafish","volume":"112","author":"Faught","year":"2022","journal-title":"Neuroendocrinology"},{"key":"B9","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1016\/j.ygcen.2005.11.005","article-title":"CRF and stress in fish","volume":"146","author":"Flik","year":"2006","journal-title":"Gen Comp Endocrinol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1023\/A:1008924418720","article-title":"Cortisol in teleosts: dynamics, mechanisms of action, and metabolic regulation","volume":"9","author":"Mommsen","year":"1999","journal-title":"Rev Fish Biol Fish"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1098\/rsos.160032","article-title":"Maternal stress-associated cortisol stimulation may protect embryos from cortisol excess in zebrafish","volume":"3","author":"Faught","year":"2016","journal-title":"R Soc Open Sci"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1113\/JP278088","article-title":"Postnatal triglyceride accumulation is regulated by mineralocorticoid receptor activation under basal and stress conditions","volume":"597","author":"Faught","year":"2019","journal-title":"J Physiol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/J.MCE.2021.111372","article-title":"Interrenal development and function in zebrafish","volume":"535","author":"Bacila","year":"2021","journal-title":"Mol Cell Endocrinol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.31428","article-title":"Mineralocorticoid receptor activates postnatal adiposity in zebrafish lacking proopiomelanocortin","volume":"239","author":"Rajeswari","year":"2024","journal-title":"J Cell Physiol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-020-0255-7","article-title":"ERK signaling: a master regulator of cell behaviour, life and fate","volume":"21","author":"Lavoie","year":"2020","journal-title":"Nat Rev Mol Cell Biol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.47.10.1549","article-title":"Epinephrine and insulin stimulate different mitogen-activated protein kinase signaling pathways in rat skeletal muscle","volume":"47","author":"Napoli","year":"1998","journal-title":"Diabetes"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M506576200","article-title":"\u03b2-arrestin-dependent, G protein-independent ERK1\/2 activation by the \u03b22 adrenergic receptor","volume":"281","author":"Shenoy","year":"2006","journal-title":"J Biol Chem"},{"key":"B18","doi-asserted-by":"publisher","first-page":"992","DOI":"10.1161\/CIRCRESAHA.108.176024","article-title":"Nuclear alpha1-adrenergic receptors signal activated ERK localization to caveolae in adult cardiac myocytes","volume":"103","author":"Wright","year":"2008","journal-title":"Circ Res"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1126\/science.1079206","article-title":"Myocyte adrenoceptor signaling pathways","volume":"300","author":"Xiang","year":"2003","journal-title":"Sci (1979)"},{"key":"B20","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/S0065-230X(08)60765-4","article-title":"Signal transduction through MAP kinase cascades","volume":"74","author":"Lewis","year":"1998","journal-title":"Adv Cancer Res"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1002\/2211-5463.13619","article-title":"Specificity models in MAPK cascade signaling","volume":"13","author":"Ma","year":"2023","journal-title":"FEBS Open Bio"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2010.12.049","article-title":"The basolateral amygdala regulates adaptation to stress via \u03b2-adrenergic receptor-mediated reductions in phosphorylated extracellular signal-regulated kinase","volume":"178","author":"Grissom","year":"2011","journal-title":"Neuroscience"},{"key":"B23","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1080\/10253890600771858","article-title":"Stress and cardiac beta adrenoceptors","volume":"9","author":"Santos","year":"2006","journal-title":"Stress"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.85.11.1092","article-title":"Recent advances in cardiac \u03b2 2 -adrenergic signal transduction","volume":"85","author":"Xiao","year":"1999","journal-title":"Circ Res"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2008.57","article-title":"Activation of ERK\/MAPK in the lateral amygdala of the mouse is required for acquisition of a fear-potentiated startle response","volume":"34","author":"Di Benedetto","year":"2009","journal-title":"Neuropsychopharmacology"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M701077200","article-title":"ERK and mTOR signaling couple \u03b2-adrenergic receptors to translation initiation machinery to gate induction of protein synthesis-dependent long-term potentiation","volume":"282","author":"Gelinas","year":"2007","journal-title":"J Biol Chem"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhv330","article-title":"\u03b2-adrenergic control of hippocampal function: subserving the choreography of synaptic information storage and memory","volume":"26","author":"Hagena","year":"2016","journal-title":"Cereb Cortex"},{"key":"B28","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1038\/npp.2016.238","article-title":"\u03b2-adrenergic receptors regulate the acquisition and consolidation phases of aversive memory formation through distinct, temporally regulated signaling pathways","volume":"42","author":"Schiff","year":"2017","journal-title":"Neuropsychopharmacology"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)81124-1","article-title":"ERK plays a regulatory role in induction of LTP by theta frequency stimulation and its modulation by \u03b2-adrenergic receptors","volume":"24","author":"Winder","year":"1999","journal-title":"Neuron"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1002\/cne.902960402","article-title":"Expression of C - fos -like protein as a marker for neuronal activity following noxious stimulation in the rat","volume":"296","author":"Bullitt","year":"1990","journal-title":"J Comp Neurology"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1111\/J.1365-2826.2008.01734.X","article-title":"Measurement of immediate-early gene activation- c-fos and beyond","volume":"20","author":"Kov\u00e1cs","year":"2008","journal-title":"J Neuroendocrinol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(88)90076-1","article-title":"The c-Fos protein interacts with c-Jun\/AP-1 to stimulate transcription of AP-1 responsive genes","volume":"54","author":"Chiu","year":"1988","journal-title":"Cell"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1242\/JCS.01589","article-title":"AP-1 subunits: quarrel and harmony among siblings","volume":"117","author":"Hess","year":"2004","journal-title":"J Cell Sci"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/J.NEUROSCIENCE.2005.12.002","article-title":"Habituation to repeated restraint stress is associated with lack of stress-induced c-fos expression in primary sensory processing areas of the rat brain","volume":"138","author":"Girotti","year":"2006","journal-title":"Neuroscience"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/J.NEUROSCIENCE.2006.07.027","article-title":"The effect of single or repeated restraint stress on several signal molecules in paraventricular nucleus, arcuate nucleus and locus coeruleus","volume":"142","author":"Kwon","year":"2006","journal-title":"Neuroscience"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.14-10-05929.1994","article-title":"Induction and habituation of immediate early gene expression in rat brain by acute and repeated restraint stress","volume":"14","author":"Melia","year":"1994","journal-title":"J Neurosci"},{"key":"B37","doi-asserted-by":"publisher","first-page":"6183","DOI":"10.1073\/PNAS.0502070102","article-title":"Corticotropin-releasing hormone activates ERK1\/2 MAPK in specific brain areas","volume":"102","author":"Refojo","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1210\/en.2008-0435","article-title":"Molecular characterization, tissue-specific expression, and regulation of melanocortin 2 receptor in rainbow trout","volume":"149","author":"Aluru","year":"2008","journal-title":"Endocrinology"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygcen.2023.114287","article-title":"Small GTPase control of pituitary hormone secretion: Evidence from studies in the goldfish (Carassius auratus) neuroendocrine model","volume":"339","author":"Khalid","year":"2023","journal-title":"Gen Comp Endocrinol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1242\/jeb.052803","article-title":"In vivo and in vitro assessment of cardiac \u03b2-adrenergic receptors in larval zebrafish (Danio rerio)","volume":"214","author":"Steele","year":"2011","journal-title":"J Exp Biol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2\u2013\u0394\u0394CT method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: an open-source platform for biological-image analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nature Methods"},{"key":"B43","doi-asserted-by":"publisher","first-page":"18081","DOI":"10.1038\/s41598-018-36681-w","article-title":"The mineralocorticoid receptor is essential for stress axis regulation in zebrafish larvae","volume":"8","author":"Faught","year":"2018","journal-title":"Sci Rep"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1007\/BF02935266","article-title":"\u03b2-Adrenergic receptor-coupled adenylate cyclase","volume":"1","author":"Sibley","year":"1987","journal-title":"Mol Neurobiol"},{"key":"B45","doi-asserted-by":"publisher","first-page":"28S","DOI":"10.1016\/S0893-133X(99)00008-1","article-title":"Serotonin and stress","volume":"21","author":"Chaouloff","year":"1999","journal-title":"Neuropsychopharmacology"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1007\/s11055-021-01099-x","article-title":"Effects of acute stress in mice with 5-HT1A receptors with different sensitivities to chronic activation by 8-OH-DPAT","volume":"51","author":"Kondaurova","year":"2021","journal-title":"Neurosci Behav Physiol"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-009-1613-5","article-title":"Dopamine D1 and D2 dopamine receptors regulate immobilization stress-induced activation of the hypothalamus-pituitary-adrenal axis","volume":"206","author":"Belda","year":"2009","journal-title":"Psychopharmacol (Berl)"},{"key":"B48","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.neubiorev.2011.04.012","article-title":"The mesoaccumbens dopamine in coping with stress","volume":"36","author":"Cabib","year":"2012","journal-title":"Neurosci Biobehav Rev"},{"key":"B49","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1079\/9781845935535.0182","article-title":"Stress response and the role of cortisol","volume":"2","author":"Vijayan","year":"2010","journal-title":"Fish Dis Disord"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2025.112494","article-title":"Brain monoamine changes modulate the corticotropin-releasing hormone receptor 1-mediated behavioral response to acute thermal stress in zebrafish larvae","volume":"600","author":"Rajeswari","year":"2025","journal-title":"Mol Cell Endocrinol"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1515\/hsz-2014-0257","article-title":"Ras activation revisited: role of GEF and GAP systems","volume":"396","author":"Hennig","year":"2015","journal-title":"Biol Chem"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1812963116","article-title":"Discovery of potent SOS1 inhibitors that block RAS activation via disruption of the RAS\u2013SOS1 interaction","volume":"116","author":"Hillig","year":"2019","journal-title":"Proc Natl Acad Sci"},{"key":"B53","doi-asserted-by":"publisher","first-page":"113322","DOI":"10.1186\/S12868-021-00653-0","article-title":"Stressor controllability modulates the stress response in fish","volume":"287","author":"Cerqueira","year":"2020","journal-title":"BMC Neurosci"},{"key":"B54","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/J.PHYSBEH.2014.12.020","article-title":"Stress and fear responses in the teleost pallium","volume":"141","author":"Silva","year":"2015","journal-title":"Physiol Behav"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.3389\/FCELL.2022.840964","article-title":"Spatial learning promotes adult neurogenesis in specific regions of the zebrafish pallium","volume":"10","author":"Mazzitelli-Fuentes","year":"2022","journal-title":"Front Cell Dev Biol"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.3389\/FNANA.2022.837527","article-title":"Integrated behavioral, genetic and brain circuit visualization methods to unravel functional anatomy of zebrafish amygdala","volume":"16","author":"Lal","year":"2022","journal-title":"Front Neuroanat"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1016\/J.YGCEN.2019.113322","article-title":"Hypothalamic- and pituitary-derived growth and reproductive hormones and the control of energy balance in fish","volume":"287","author":"Blanco","year":"2020","journal-title":"Gen Comp Endocrinol"},{"key":"B58","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1080\/10408440601123529","article-title":"The hypothalamic-pituitary-thyroid (HPT) axis in fish and its role in fish development and reproduction","volume":"37","author":"Blanton","year":"2007","journal-title":"Crit Rev Toxicol"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.3389\/FENDO.2014.00036","article-title":"Central pathways integrating metabolism and reproduction in teleosts","volume":"5","author":"Shahjahan","year":"2014","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B60","doi-asserted-by":"publisher","first-page":"1497","DOI":"10.1016\/J.CUB.2022.02.011","article-title":"Hypothalamic Galanin-producing neurons regulate stress in zebrafish through a peptidergic, self-inhibitory loop","volume":"32","author":"Corradi","year":"2022","journal-title":"Curr Biol"},{"key":"B61","doi-asserted-by":"publisher","first-page":"959","DOI":"10.1038\/S41593-020-0655-1","article-title":"Multiple convergent hypothalamus-brainstem circuits drive defensive behavior","volume":"23","author":"Lovett-Barron","year":"2020","journal-title":"Nat Neurosci"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1016\/J.XPRO.2022.101731","article-title":"Using pERK immunostaining to quantify neuronal activity induced by stress in zebrafish larvae","volume":"3","author":"Corradi","year":"2022","journal-title":"STAR Protoc"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00096.2002","article-title":"Duality of G protein-coupled mechanisms for \u03b2-adrenergic activation of NKCC activity in skeletal muscle","volume":"283","author":"Gosmanov","year":"2002","journal-title":"Am J Physiology-Cell Physiol"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.102.037531","article-title":"Relationship between \u03b11-adrenergic receptor-induced contraction and extracellular signal-regulated kinase activation in the bovine inferior alveolar artery","volume":"303","author":"Hague","year":"2002","journal-title":"J Pharmacol Exp Ther"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1074\/JBC.272.31.19125","article-title":"Ras-dependent mitogen-activated protein kinase activation by G protein-coupled receptors. Convergence of Gi- and Gq-mediated pathways on calcium\/calmodulin, Pyk2, and Src kinase","volume":"272","author":"Della Rocca","year":"1997","journal-title":"J Biol Chem"},{"key":"B66","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1210\/ME.2012-1359","article-title":"B-raf and CRHR1 internalization mediate biphasic ERK1\/2 activation by CRH in hippocampal HT22 cells","volume":"27","author":"Bonfiglio","year":"2013","journal-title":"Mol Endocrinology"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.09.037","article-title":"CRH promotes the neurogenic activity of neural stem cells in the adult hippocampus","volume":"29","author":"Koutmani","year":"2019","journal-title":"Cell Rep"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.3389\/fmars.2023.1184792","article-title":"Functional characterization of two corticotropin-releasing hormone receptors in Larimichthys crocea","volume":"10","author":"Liu","year":"2023","journal-title":"Front Mar Sci"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2015.07.002","article-title":"CRH engagement of the locus coeruleus noradrenergic system mediates stress-induced anxiety","volume":"87","author":"McCall","year":"2015","journal-title":"Neuron"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2830-04.2004","article-title":"Corticotropin-releasing hormone directly activates noradrenergic neurons of the locus ceruleus recorded","volume":"24","author":"Jedema","year":"2004","journal-title":"In Vitro. J Neurosci"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2011.218","article-title":"Corticotropin-releasing factor in the norepinephrine nucleus, locus coeruleus, facilitates behavioral flexibility","volume":"37","author":"Snyder","year":"2012","journal-title":"Neuropsychopharmacology"},{"key":"B72","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1016\/j.ejphar.2007.11.062","article-title":"Convergent regulation of locus coeruleus activity as an adaptive response to stress","volume":"583","author":"Valentino","year":"2008","journal-title":"Eur J Pharmacol"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1336-08.2008","article-title":"Corticotropin-releasing factor in the basolateral amygdala enhances memory consolidation via an interaction with the -adrenoceptor-cAMP pathway: dependence on glucocorticoid receptor activation","volume":"28","author":"Roozendaal","year":"2008","journal-title":"J Neurosci"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1152\/PHYSREV.00056.2021","article-title":"Windows into stress: a glimpse at emerging roles for CRHPVN neurons","volume":"103","author":"Rasiah","year":"2023","journal-title":"Physiol Rev"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1111\/JNE.13268","article-title":"Hypothalamic corticotrophin releasing hormone neurons in stress-induced psychopathology: Revaluation of synaptic contributions","volume":"35","author":"Stanton","year":"2023","journal-title":"J Neuroendocrinol"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1006\/GCEN.2001.7707","article-title":"Central administration of corticotropin-releasing hormone stimulates locomotor activity in juvenile chinook salmon (Oncorhynchus tshawytscha)","volume":"125","author":"Clements","year":"2002","journal-title":"Gen Comp Endocrinol"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1016\/J.YHBEH.2007.07.012","article-title":"Corticotropin releasing factor induces anxiogenic locomotion in trout and alters serotonergic and dopaminergic activity","volume":"52","author":"Carpenter","year":"2007","journal-title":"Horm Behav"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11937","article-title":"Hypothalamic CRH neurons orchestrate complex behaviours after stress","volume":"7","author":"F\u00fczesi","year":"2016","journal-title":"Nat Commun"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1242\/jeb.245859","article-title":"Evolution and divergence of teleost adrenergic receptors: why sometimes \u2018the drugs don\u2019t work\u2019 in fish","volume":"226","author":"Joyce","year":"2023","journal-title":"J Exp Biol"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-0618(97)00042-2","article-title":"Distribution of \u03b11a-, \u03b11b- and \u03b11d-adrenergic receptor mRNA in the rat brain and spinal cord","volume":"13","author":"Day","year":"1997","journal-title":"J Chem Neuroanat"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1124\/mol.111.073734","article-title":"Long-term \u03b11A-adrenergic receptor stimulation improves synaptic plasticity, cognitive function, mood, and longevity","volume":"80","author":"Doze","year":"2011","journal-title":"Mol Pharmacol"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1186\/s13041-021-00895-3","article-title":"Stress-induced antinociception to noxious heat requires \u03b11A-adrenaline receptors of spinal inhibitory neurons in mice","volume":"15","author":"Uchiyama","year":"2022","journal-title":"Mol Brain"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1002\/(sici)1096-9861(19970929)386:3<358::aid-cne3>3.0.co;2-0","article-title":"Distribution of alpha1A adrenergic receptor mRNA in the rat brain visualized by in situ hybridization","volume":"386","author":"Domyancic","year":"1997","journal-title":"J Comp Neurol"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.2174\/157015909790031193","article-title":"Neuroplasticity regulation by noradrenaline in mammalian brain","volume":"7","author":"Marzo","year":"2009","journal-title":"Curr Neuropharmacol"},{"key":"B85","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/j.eplepsyres.2008.12.007","article-title":"Alpha-1A adrenergic receptor activation increases inhibitory tone in CA1 hippocampus","volume":"84","author":"Hillman","year":"2009","journal-title":"Epilepsy Res"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-0186(99)00077-7","article-title":"Localization of \u03b11B-adrenergic receptor in female rat brain regions involved in stress and neuroendocrine function","volume":"35","author":"Acosta-Martinez","year":"1999","journal-title":"Neurochem Int"},{"key":"B87","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1016\/J.YNSTR.2018.02.001","article-title":"c-Fos mapping of brain regions activated by multi-modal and electric foot shock stress","volume":"8","author":"Lin","year":"2018","journal-title":"Neurobiol Stress"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1126\/SCIADV.ADE9909\/SUPPL_FILE\/SCIADV.ADE9909_MOVIES_S1_TO_S3.ZIP","article-title":"A single-cell resolution gene expression atlas of the larval zebrafish brain","volume":"9","author":"Shainer","year":"2023","journal-title":"Sci Adv"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1007\/s12576-009-0044-8","article-title":"c-Fos expression in the supraoptic nucleus is the most intense during different durations of restraint water-immersion stress in the rat","volume":"59","author":"Zhang","year":"2009","journal-title":"J Physiol Sci"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05343-3","article-title":"Non-canonical \u03b2-adrenergic activation of ERK at endosomes","volume":"611","author":"Kwon","year":"2022","journal-title":"Nature"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1006\/mcne.2002.1188","article-title":"Phosphorylation of Hippocampal Erk-1\/2, Elk-1, and p90-Rsk-1 during Contextual Fear Conditioning: Interactions between Erk-1\/2 and Elk-1","volume":"21","author":"Sananbenesi","year":"2002","journal-title":"Mol Cell Neurosci"},{"key":"B92","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.3724\/ABBS.2022096","article-title":"Gi-protein-coupled \u03b2 1-adrenergic receptor: re-understanding the selectivity of \u03b2 1-adrenergic receptor to G protein: Gi-protein-coupled \u03b2 1-adrenergic receptor","volume":"54","author":"Chen","year":"2022","journal-title":"Acta Biochim Biophys Sin (Shanghai)"},{"key":"B93","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1111\/J.1476-5381.2011.01631.X","article-title":"Insights into mechanisms of corticotropin-releasing hormone receptor signal transduction","volume":"166","author":"Grammatopoulos","year":"2012","journal-title":"Br J Pharmacol"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.124.323067","article-title":"G protein-coupled receptors: A century of research and discovery","volume":"135","author":"Liu","year":"2024","journal-title":"Circ Res"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.1210\/JC.2011-3383","article-title":"CRH activation of different signaling pathways results in differential calcium signaling in human pregnant myometrium before and during labor","volume":"97","author":"You","year":"2012","journal-title":"J Clin Endocrinol Metab"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.1016\/BS.IRCMB.2018.02.004","article-title":"Spatiotemporal modulation of ERK activation by GPCRs","volume":"338","author":"Watson","year":"2018","journal-title":"Int Rev Cell Mol Biol"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2017.07.016","article-title":"Tracing information flow from erk to target gene induction reveals mechanisms of dynamic and combinatorial control","volume":"67","author":"Wilson","year":"2017","journal-title":"Mol Cell"},{"key":"B98","doi-asserted-by":"publisher","first-page":"16670","DOI":"10.1038\/s41598-019-52997-7","article-title":"Social defeat stress-specific increase in c-Fos expression in the extended amygdala in mice: Involvement of dopamine D1 receptor in the medial prefrontal cortex","volume":"9","author":"Numa","year":"2019","journal-title":"Sci Rep"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2005.12.021","article-title":"5-HT1A receptor activation counteracts c-Fos immunoreactivity induced in serotonin neurons of the raphe nuclei after immobilization stress in the male rat","volume":"397","author":"Rioja","year":"2006","journal-title":"Neurosci Lett"},{"key":"B100","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1007\/S00221-009-1862-X","article-title":"Dopamine and inhibitory action control: evidence from spontaneous eye blink rates","volume":"196","author":"Colzato","year":"2009","journal-title":"Exp Brain Res Experimentelle Hirnforschung Experimentation Cerebrale"},{"key":"B101","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/J.CORTEX.2019.01.016","article-title":"Dopamine effects on frontal cortical blood flow and motor inhibition in parkinson\u2019s disease","volume":"115","author":"Trujillo","year":"2019","journal-title":"Cortex"},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.1016\/J.CUB.2016.06.041","article-title":"The basal ganglia over 500 million years","volume":"26","author":"Grillner","year":"2016","journal-title":"Curr Biol"},{"key":"B103","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/J.BRAINRES.2012.02.022","article-title":"Distinct models of induced hyperactivity in zebrafish larvae","volume":"1449","author":"Ellis","year":"2012","journal-title":"Brain Res"},{"key":"B104","doi-asserted-by":"publisher","DOI":"10.1016\/J.YGCEN.2008.09.011","article-title":"The zebrafish stress axis: Molecular fallout from the teleost-specific genome duplication event","volume":"161","author":"Alsop","year":"2009","journal-title":"Gen Comp Endocrinol"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1650458\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T04:13:44Z","timestamp":1757564024000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1650458\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,11]]},"references-count":104,"alternative-id":["10.3389\/fendo.2025.1650458"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2025.1650458","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,11]]},"article-number":"1650458"}}