{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T20:43:02Z","timestamp":1768509782922,"version":"3.49.0"},"posted":{"date-parts":[[2024,2,12]]},"group-title":"Neuroscience","reference-count":60,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,2,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Environmental stimuli elicit drug craving and relapse in cocaine users by triggering the retrieval of strong cocaine-related contextual memories. Retrieval can also destabilize drug memories, requiring reconsolidation, a protein synthesis-dependent storage process, to maintain memory strength. Corticotropin-releasing factor (CRF) signaling in the basolateral amygdala (BLA) is necessary for cocaine-memory reconsolidation. We have hypothesized that a critical source of CRF in the BLA is the dorsal raphe nucleus (DR) based on its neurochemistry, anatomical connectivity, and requisite involvement in cocaine-memory reconsolidation. To test this hypothesis, male and female Sprague-Dawley rats received adeno-associated viruses to express Gi-coupled designer receptors exclusively activated by designer drugs (DREADDs) selectively in CRF neurons of the DR and injection cannulae directed at the BLA. The rats were trained to self-administer cocaine in a distinct environmental context then received extinction training in a different context. They were then briefly re-exposed to the cocaine-predictive context to destabilize (reactivate) cocaine memories. Intra-BLA infusions of the DREADD agonist deschloroclozapine (DCZ; 0.1 mM, 0.5 \u03bcL\/hemisphere) after memory reactivation attenuated cocaine-memory strength, relative to vehicle infusion. This was indicated by a selective, DCZ-induced and memory reactivation-dependent decrease in drug-seeking behavior in the cocaine-predictive context in DREADD-expressing males and females at test compared to respective controls. Notably, BLA-projecting DR CRF neurons that exhibited increased c-Fos expression during memory reconsolidation co-expressed glutamatergic and serotonergic neuronal markers. Together, these findings suggest that the DR\n                  <jats:sub>CRF<\/jats:sub>\n                  \u2192 BLA circuit is engaged to maintain cocaine-memory strength after memory destabilization, and this phenomenon may be mediated by DR CRF, glutamate, and\/or serotonin release in the BLA.\n                <\/jats:p>","DOI":"10.1101\/2024.02.10.579725","type":"posted-content","created":{"date-parts":[[2024,2,12]],"date-time":"2024-02-12T15:50:13Z","timestamp":1707753013000},"source":"Crossref","is-referenced-by-count":0,"title":["Dorsal Raphe to Basolateral Amygdala Corticotropin-Releasing Factor Circuit Regulates Cocaine-Memory Reconsolidation"],"prefix":"10.64898","author":[{"given":"Jobe L.","family":"Ritchie","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuyi","family":"Qi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David A.","family":"Soto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sydney E.","family":"Swatzell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hope I.","family":"Grenz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Avery Y.","family":"Pruitt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lilia M.","family":"Artimenia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Spencer K.","family":"Cooke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Craig W.","family":"Berridge","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5999-9969","authenticated-orcid":false,"given":"Rita A.","family":"Fuchs","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024021511400474000_2024.02.10.579725v1.1","doi-asserted-by":"publisher","DOI":"10.1037\/\/0097-7403.12.4.333"},{"key":"2024021511400474000_2024.02.10.579725v1.2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1992.tb25984.x"},{"key":"2024021511400474000_2024.02.10.579725v1.3","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2090"},{"key":"2024021511400474000_2024.02.10.579725v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2005.08.007"},{"key":"2024021511400474000_2024.02.10.579725v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2005.08.006"},{"key":"2024021511400474000_2024.02.10.579725v1.6","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-013-3039-3"},{"key":"2024021511400474000_2024.02.10.579725v1.7","doi-asserted-by":"crossref","first-page":"104283","DOI":"10.1016\/j.ebiom.2022.104283","article-title":"The effect of a methadone-initiated memory reconsolidation updating procedure in opioid use disorder: A translational study","volume":"85","year":"2022","journal-title":"EBioMedicine"},{"issue":"3","key":"2024021511400474000_2024.02.10.579725v1.8","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1001\/jamapsychiatry.2016.3907","article-title":"Effect of Selective Inhibition of Reactivated Nicotine-Associated Memories With Propranolol on Nicotine Craving","volume":"74","year":"2017","journal-title":"JAMA Psychiatry"},{"key":"2024021511400474000_2024.02.10.579725v1.9","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.jbtep.2015.09.012","article-title":"Reactivating addiction-related memories under propranolol to reduce craving: A pilot randomized controlled trial","volume":"50","year":"2016","journal-title":"J Behav Ther Exp Psychiatry"},{"key":"2024021511400474000_2024.02.10.579725v1.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2012.02.004"},{"key":"2024021511400474000_2024.02.10.579725v1.11","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2009.06888.x"},{"key":"2024021511400474000_2024.02.10.579725v1.12","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3149-09.2010"},{"key":"2024021511400474000_2024.02.10.579725v1.13","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-013-3203-9"},{"key":"2024021511400474000_2024.02.10.579725v1.14","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2012.238"},{"key":"2024021511400474000_2024.02.10.579725v1.15","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0323-06.2006"},{"key":"2024021511400474000_2024.02.10.579725v1.16","doi-asserted-by":"crossref","unstructured":"Ritchie JL , Walters, J. 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