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Dysregulation of the LC\u2010NE system is strongly linked with several stress\u2010induced neuropsychiatric disorders, highlighting the LC's pivotal role in the development of these disorders. Located in the dorsal pontine tegmental area, the LC contains noradrenergic neurons that serve as the main source of NE in the central nervous system. Activation of the LC and subsequent release of NE at different levels of the neuroaxis is adaptive, allowing the body to adjust appropriately amid a challenging stimulus. However, prolonged and repeated LC activation leads to maladaptive responses that implicate LC\u2010NE dysfunction in stress\u2010induced neuropsychiatric disorders. As the primary initiator of the stress response, corticotropin\u2010releasing factor (CRF) activates the hypothalamic\u2013pituitary\u2013adrenal axis. Following the discovery of CRF more than four decades ago, numerous studies established that CRF also acts as a neurotransmitter that governs the activity of other neurotransmitters in the brain neurotransmitter system. The LC\u2010NE system receives abundant CRF afferents arising from several brain nuclei. CRF afferents to LC\u2010NE are activated and recruited in the pathogenesis of stress\u2010induced neuropsychiatric disorders. Presented in this review are the CRF neuroanatomical connectivity and physiological characteristics that modulate LC\u2010NE function, which may contribute to the pathogenesis of stress\u2010induced neuropsychiatric disorders. Additionally, this review illustrates the contribution of LC\u2010NE to the apparent sex\u2010dependent differences in stress\u2010induced neuropsychiatric disorders. Hence, the LC\u2010NE system is a promising target for the development of therapeutic strategies for stress\u2010induced neuropsychiatric disorders.<\/jats:p>","DOI":"10.1111\/ejn.70111","type":"journal-article","created":{"date-parts":[[2025,4,12]],"date-time":"2025-04-12T04:44:11Z","timestamp":1744433051000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["The Locus Coeruleus: Anatomy, Physiology, and Stress\u2010Related Neuropsychiatric Disorders"],"prefix":"10.1111","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-9694-2278","authenticated-orcid":false,"given":"Beverly\u00a0A.\u00a0S.","family":"Reyes","sequence":"first","affiliation":[{"name":"Department of Pharmacology &amp; Physiology Drexel University College of Medicine  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,4,12]]},"reference":[{"key":"e_1_2_18_2_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.07-09-02837.1987"},{"key":"e_1_2_18_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2014.02.032"},{"key":"e_1_2_18_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2312662120"},{"key":"e_1_2_18_5_1","unstructured":"Alcoholism NIAAA. 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