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Contexts surrounding drug use integrate this aberrant mnemonic process and hold strong relapse-triggering ability. Here, we asked where context and salience might be concurrently represented in the brain during retrieval of drug\u2013context paired associations. For this, we developed a morphine-conditioned place preference protocol that allows contextual stimuli presentation inside a magnetic resonance imaging scanner and investigated differences in activity and connectivity at context recall. We found context-specific responses to stimulus onset in multiple brain regions, namely, limbic, sensory and striatal. Differences in functional interconnectivity were found among amygdala, lateral habenula, and lateral septum. We also investigated alterations to resting-state functional connectivity and found increased centrality of the lateral septum in a proposed limbic network, as well as increased functional connectivity of the lateral habenula and hippocampal \u2018cornu ammonis\u2019 1 region, after a protocol of associative drug\u2013context. Finally, we found that pre- conditioned place preference resting-state connectivity of the lateral habenula and amygdala was predictive of inter-individual conditioned place preference score differences. Overall, our findings show that drug and saline-paired contexts establish distinct memory traces in overlapping functional brain microcircuits and that intrinsic connectivity of the habenula, septum, and amygdala likely underlies the individual maladaptive contextual learning to opioid exposure. We have identified functional maps of acquisition and retrieval of drug-related memory that may support the relapse-triggering ability of opioid-associated sensory and contextual cues. These findings may clarify the inter-individual sensitivity and vulnerability seen in addiction to opioids found in humans.<\/jats:p>","DOI":"10.1093\/braincomms\/fcae281","type":"journal-article","created":{"date-parts":[[2024,8,19]],"date-time":"2024-08-19T07:44:14Z","timestamp":1724053454000},"source":"Crossref","is-referenced-by-count":1,"title":["Mapping functional traces of opioid memories in the rat brain"],"prefix":"10.1093","volume":"6","author":[{"given":"Joana","family":"Gomes-Ribeiro","sequence":"first","affiliation":[{"name":"Instituto de Medicina Molecular Jo\u00e3o Lobo Antunes, Faculdade de Medicina de Lisboa, Universidade de Lisboa , 1649-028 Lisboa ,","place":["Portugal"]}]},{"given":"Jo\u00e3o","family":"Martins","sequence":"additional","affiliation":[{"name":"Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), Institute for Nuclear Sciences Applied to Health (ICNAS), University of Coimbra , 3000-548 Coimbra ,","place":["Portugal"]}]},{"given":"Jos\u00e9","family":"Sereno","sequence":"additional","affiliation":[{"name":"Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), Institute for Nuclear Sciences Applied to Health (ICNAS), University of Coimbra , 3000-548 Coimbra ,","place":["Portugal"]},{"name":"CQC, Chemistry Department, University of Coimbra , 3004-535 Coimbra ,","place":["Portugal"]}]},{"given":"Samuel","family":"Deslauriers-Gauthier","sequence":"additional","affiliation":[{"name":"Centre Inria d'Universit\u00e9 C\u00f4te d'Azur , 06902 Valbonne ,","place":["France"]}]},{"given":"Teresa","family":"Summavielle","sequence":"additional","affiliation":[{"name":"Addiction Biology Group, i3S- Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), Universidade do Porto , 4200-135 Porto ,","place":["Portugal"]},{"name":"ESS, Polytechnic of Porto , 4200-072 Porto ,","place":["Portugal"]}]},{"given":"Joana E","family":"Coelho","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular Jo\u00e3o Lobo Antunes, Faculdade de Medicina de Lisboa, Universidade de Lisboa , 1649-028 Lisboa ,","place":["Portugal"]}]},{"given":"Miguel","family":"Remondes","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular Jo\u00e3o Lobo Antunes, Faculdade de Medicina de Lisboa, Universidade de Lisboa , 1649-028 Lisboa ,","place":["Portugal"]},{"name":"Faculdade de Medicina Veterin\u00e1ria, Universidade Lus\u00f3fona , 1749-024 Lisboa ,","place":["Portugal"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4364-6373","authenticated-orcid":false,"given":"Miguel","family":"Castelo-Branco","sequence":"additional","affiliation":[{"name":"Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), Institute for Nuclear Sciences Applied to Health (ICNAS), University of Coimbra , 3000-548 Coimbra ,","place":["Portugal"]},{"name":"Faculty of Medicine, University of Coimbra , 3000-370 Coimbra ,","place":["Portugal"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8367-3005","authenticated-orcid":false,"given":"Lu\u00edsa V","family":"Lopes","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular Jo\u00e3o Lobo Antunes, Faculdade de Medicina de Lisboa, Universidade de Lisboa , 1649-028 Lisboa ,","place":["Portugal"]}]}],"member":"286","published-online":{"date-parts":[[2024,8,19]]},"reference":[{"issue":"6","key":"2024103011282837600_fcae281-B1","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1111\/add.14940","article-title":"Impact of opioid dose escalation on the development of substance use disorders, accidents, self-inflicted injuries, opioid overdoses and alcohol and non-opioid drug-related overdoses: A retrospective cohort 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