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Adverse experiences of early-life stress (ELS) are prominent risk factors for the precipitation of major depressive disorder (MDD). In recent years, dysfunction of the central noradrenergic (NA) system and subsequent deficits in norepinephrine (NE) signaling have gained increasing attention in the pathophysiology of MDD. However, the role of the \u03b1-2A adrenergic receptor and its downstream second messenger signaling system has not been investigated in connection to early-life stress-induced depression, limiting valuable insights into neurobiological mechanisms underlying this disorder. In this study, we used maternal separation (MS) as a rodent model of ELS to investigate whether ELS-induced depressive behavior is related to the \u03b1-2A adrenergic receptor and its associated second messenger signaling cascade. To do so, we studied expression levels of the \u03b1-2A adrenergic receptor (\n                    <jats:italic>Adra2a<\/jats:italic>\n                    ), G alpha proteins (stimulatory subunit-G\n                    <jats:sub>\u03b1s<\/jats:sub>\n                    [\n                    <jats:italic>Gnas<\/jats:italic>\n                    ] and inhibitory subunit-G\n                    <jats:sub>\u03b1i<\/jats:sub>\n                    [\n                    <jats:italic>Gnai1<\/jats:italic>\n                    and\n                    <jats:italic>Gnai2<\/jats:italic>\n                    ]), and downstream protein kinase A (PKA) catalytic [\n                    <jats:italic>Prkarc<\/jats:italic>\n                    \u03b1 and\n                    <jats:italic>Prkarc\u03b2<\/jats:italic>\n                    ] and regulatory subunits [\n                    <jats:italic>Prkar1\u03b1<\/jats:italic>\n                    ,\n                    <jats:italic>Prkar1\u03b2<\/jats:italic>\n                    ,\n                    <jats:italic>Prkar2\u03b1<\/jats:italic>\n                    , and\n                    <jats:italic>Prkar2\u03b2<\/jats:italic>\n                    ]) in the frontal cortex (FC) of MS rats. We found reduced sucrose preference in MS animals, along with reduced transcript levels of\n                    <jats:italic>Adra2a<\/jats:italic>\n                    ,\n                    <jats:italic>Gnai2<\/jats:italic>\n                    ,\n                    <jats:italic>Prkar1\u03b2<\/jats:italic>\n                    , and\n                    <jats:italic>Prkarc\u03b2<\/jats:italic>\n                    . These findings suggest that ELS exposure may contribute to depression symptomatology via alterations in the expression of key genes involved in the NA system, highlighting potential mechanisms underlying ELS-induced depressive behavior.\n                  <\/jats:p>","DOI":"10.1007\/s12035-024-04578-7","type":"journal-article","created":{"date-parts":[[2024,11,12]],"date-time":"2024-11-12T20:03:53Z","timestamp":1731441833000},"page":"5297-5310","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Early-Life Stress Influences the Transcriptional Activation of Alpha-2A Adrenergic Receptor and Associated Protein Kinase A Signaling Molecules in the Frontal Cortex of Rats"],"prefix":"10.1007","volume":"62","author":[{"given":"Sarah","family":"Ali","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5359-4717","authenticated-orcid":false,"given":"Yogesh","family":"Dwivedi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,11,13]]},"reference":[{"issue":"3","key":"4578_CR1","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1007\/s00406-005-0624-4","volume":"256","author":"RF Anda","year":"2006","unstructured":"Anda RF, Felitti VJ, Bremner JD, Walker JD, Whitfield C, Perry BD, Dube SR, Giles WH (2006) The enduring effects of abuse and related adverse experiences in childhood. 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