{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:29:14Z","timestamp":1785421754765,"version":"3.56.0"},"reference-count":37,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000025","name":"NIH","doi-asserted-by":"publisher","award":["MH132052"],"award-info":[{"award-number":["MH132052"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000025","name":"NIH","doi-asserted-by":"publisher","award":["T32DA007237"],"award-info":[{"award-number":["T32DA007237"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]},{"award":["MH132052"],"award-info":[{"award-number":["MH132052"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["T32DA007237"],"award-info":[{"award-number":["T32DA007237"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000874","name":"Brain and Behavior Research Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000874","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/03a63f080","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Background\/Objectives: Dopamine is well known for its role in reward learning, where phasic activity encodes prediction errors and supports the formation of cue\u2013outcome associations. More recently, dopamine has been implicated in encoding salience, novelty, and aversive events, suggesting a broader function in shaping learning and memory across motivational contexts. However, how accumbal dopamine contributes to the recovery of extinguished fear, a process central to relapse in anxiety and trauma-related disorders, remains unclear. Methods: Here, we examined NAc core dopamine dynamics during shock-induced reinstatement of an extinguished fear memory. Using dLight fiber photometry, we found that a sustained decrease in baseline dopamine marked extinction recall. In contrast, an unexpected reminder footshock prevented this reduction, maintaining dopamine levels near baseline as freezing behavior re-emerged. Results: The reminder shock also evoked a transient dopamine peak, and optogenetic manipulations demonstrated that dopamine signaling during this period bidirectionally modulated reinstatement, with enhancement of dopamine release increasing reinstatement and inhibition of dopamine terminals markedly attenuating it. Together, these results demonstrate that unexpected aversive events reset NAc core dopamine levels and gate the return of extinguished fear. Conclusions: By revealing that accumbal dopamine contributes to fear recovery, this work broadens current models of dopamine function and identifies a neural mechanism through which surprising events may promote relapse of aversive memories in anxiety- and stress-related disorders.<\/jats:p>","DOI":"10.3390\/brainsci16070690","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T08:26:15Z","timestamp":1782807975000},"page":"690","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dopamine Response to Unexpected Aversive Outcomes Drives the Return of Extinguished Fear"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-5647-5457","authenticated-orcid":false,"given":"Bhumiben P.","family":"Patel","sequence":"first","affiliation":[{"name":"Center for Substance Abuse Research, Temple University Lewis Katz School of Medicine, University in Philadelphia, Philadelphia, PA 19140, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Tat","sequence":"additional","affiliation":[{"name":"University of Tennessee Health Science Center, Memphis, TN 38163, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3803-974X","authenticated-orcid":false,"given":"Oyku","family":"Dinckol","sequence":"additional","affiliation":[{"name":"Center for Substance Abuse Research, Temple University Lewis Katz School of Medicine, University in Philadelphia, Philadelphia, PA 19140, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6545-3616","authenticated-orcid":false,"given":"Noah Harris","family":"Wenger","sequence":"additional","affiliation":[{"name":"Center for Substance Abuse Research, Temple University Lewis Katz School of Medicine, University in Philadelphia, Philadelphia, PA 19140, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8489-582X","authenticated-orcid":false,"given":"Aryanna","family":"Copling","sequence":"additional","affiliation":[{"name":"Center for Substance Abuse Research, Temple University Lewis Katz School of Medicine, University in Philadelphia, Philadelphia, PA 19140, USA"},{"name":"Biomedical Sciences Graduate Program, Temple University Lewis Katz School of Medicine, University in Philadelphia, Philadelphia, PA 19140, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2700-977X","authenticated-orcid":false,"given":"Munir Gunes","family":"Kutlu","sequence":"additional","affiliation":[{"name":"Center for Substance Abuse Research, Temple University Lewis Katz School of Medicine, University in Philadelphia, Philadelphia, PA 19140, USA"},{"name":"Department of Neural Sciences, Temple University Lewis Katz School of Medicine, University in Philadelphia, Philadelphia, PA 19140, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1126\/science.275.5306.1593","article-title":"A Neural Substrate of Prediction and Reward","volume":"275","author":"Schultz","year":"1997","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1016\/j.neuron.2010.11.022","article-title":"Dopamine in Motivational Control: Rewarding, Aversive, and Alerting","volume":"68","author":"Matsumoto","year":"2010","journal-title":"Neuron"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"15647","DOI":"10.1073\/pnas.1014269108","article-title":"Understanding Dopamine and Reinforcement Learning: The Dopamine Reward Prediction Error Hypothesis","volume":"108","author":"Glimcher","year":"2011","journal-title":"Proc. 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