{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:07:03Z","timestamp":1785434823938,"version":"3.56.0"},"posted":{"date-parts":[[2026,6,26]]},"group-title":"Neuroscience","reference-count":53,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T00:00:00Z","timestamp":1782432000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"award":["R01AA021505"],"award-info":[{"award-number":["R01AA021505"]}],"id":[{"id":"https:\/\/ror.org\/02jzrsm59","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01AA027768"],"award-info":[{"award-number":["R01AA027768"]}],"id":[{"id":"https:\/\/ror.org\/02jzrsm59","id-type":"ROR","asserted-by":"publisher"}]},{"award":["U01AA025932"],"award-info":[{"award-number":["U01AA025932"]}],"id":[{"id":"https:\/\/ror.org\/02jzrsm59","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,6,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Opioid withdrawal is a powerful negative affective state that promotes continued drug use and relapse, and is often associated with hypodopaminergic states. Although corticotropin-releasing factor (CRF) signaling in the extended amygdala has been strongly implicated in stress and negative affect, how withdrawal-recruited CRF systems suppress dopamine release remains poorly understood. Here, we identify an extended amygdala\u2013striosome\u2013dopamine pathway engaged during fentanyl withdrawal. Naloxone-precipitated fentanyl withdrawal selectively recruited CRF neurons in the central amygdala and bed nucleus of the stria terminalis. These CRF neurons provided monosynaptic input to dorsostriatal medium spiny neurons (MSNs). Because striosomal MSNs are positioned to regulate dopamine release, we next found that CRF enhanced glutamatergic synaptic transmission onto striosomal MSNs, with CRF receptor 1 (CRFR1) signaling required for the postsynaptic strengthening of excitatory transmission. In vivo dopamine photometry further revealed that naloxone-precipitated withdrawal amplified striosome-mediated suppression of dopamine release, and this amplification was prevented by CRFR1 antagonism. Together, these findings reveal a mechanism by which withdrawal-recruited CRF signaling potentiates striosomal control of dopamine release. This extended amygdala\u2013striosome\u2013dopamine pathway may contribute to the hypodopaminergic negative affective state that drives opioid withdrawal and relapse vulnerability.<\/jats:p>\n                <jats:sec>\n                  <jats:title>Highlights<\/jats:title>\n                  <jats:list list-type=\"bullet\">\n                    <jats:list-item>\n                      <jats:p>Fentanyl withdrawal selectively recruits CeA and BNST CRF neurons<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>CeA and BNST CRF neurons provide monosynaptic input to striatal MSNs<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>CRF potentiates glutamatergic transmission onto striosomal MSNs via CRFR1<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>CRFR1 signaling amplifies striosome-mediated dopamine suppression during withdrawal<\/jats:p>\n                    <\/jats:list-item>\n                  <\/jats:list>\n                <\/jats:sec>","DOI":"10.64898\/2026.06.22.733757","type":"posted-content","created":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T12:20:20Z","timestamp":1782562820000},"source":"Crossref","is-referenced-by-count":0,"title":["Extended Amygdala CRF Projections to Striatal Striosomes Potentiate Dopamine Suppression During Fentanyl Withdrawal"],"prefix":"10.64898","author":[{"given":"Xueyi","family":"Xie","sequence":"first","affiliation":[{"name":"Department of Neuroscience and Experimental Therapeutics, College of Medicine, Texas A&M University Health Science Center, Bryan, Texas 77807"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Essoh","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Experimental Therapeutics, College of Medicine, Texas A&M University Health 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