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Beyond regulating haemodynamics, AT1R activation in the central nervous system (CNS) modulates neuroinflammatory cascades, dopaminergic signalling plasticity, and stress\u2010responsive neural circuit processes central to addiction pathophysiology. Notably, preclinical studies reveal that AT1R blockade attenuates drug\u2010seeking behaviours by normalizing mesolimbic dopamine dysregulation and reducing glutamatergic excitotoxicity in the nucleus accumbens. This review systematically integrates contemporary evidence elucidating the dual pathophysiological roles of AT1R in CNS disorders, with particular emphasis on neurodegenerative diseases and psychiatric conditions. Crucially, we delineate two mechanistically distinct yet interconnected functions of AT1R: (1) serving as a critical mediator of maladaptive neuroplasticity during protracted exposure to addictive substances and (2) functioning as a regulator of blood\u2013brain barrier (BBB) integrity, thereby potentiating neurotoxicant infiltration in substance use disorders. Building upon these mechanistic insights, we propose a translational framework for repurposing clinically approved AT1R antagonists as novel pharmacotherapies targeting addiction\u2010related neurocircuitry dysregulation. By bridging molecular insights with translational opportunities, this work positions AT1R as a novel therapeutic target to address unmet clinical needs in addiction.<\/jats:p>","DOI":"10.1111\/adb.70152","type":"journal-article","created":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T11:01:43Z","timestamp":1776164503000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["AT1R in Central Nervous System Disorders: Unveiling Novel Mechanisms and Therapeutic Avenues for Addiction"],"prefix":"10.1111","volume":"31","author":[{"given":"Jianan","family":"Lv","sequence":"first","affiliation":[{"name":"School of Pharmacy, Health Science Center Ningbo University  Ningbo China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Zhu","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Health Science Center Ningbo University  Ningbo 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