{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T05:35:04Z","timestamp":1778132104922,"version":"3.51.4"},"reference-count":74,"publisher":"Society for Neuroscience","issue":"4","license":[{"start":{"date-parts":[[2021,7,27]],"date-time":"2021-07-27T00:00:00Z","timestamp":1627344000000},"content-version":"vor","delay-in-days":239,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"funder":[{"name":"NIH NIDA","award":["F31 DA045430"],"award-info":[{"award-number":["F31 DA045430"]}]},{"name":"NIH NIDA","award":["R01 DA025646"],"award-info":[{"award-number":["R01 DA025646"]}]},{"name":"NIH NINDS","award":["T32 NS007431"],"award-info":[{"award-number":["T32 NS007431"]}]},{"name":"NIH NIAAA","award":["R01 AA026078"],"award-info":[{"award-number":["R01 AA026078"]}]},{"name":"WA I-171 funds administered through the Washington State University Alcohol and Drug Abuse Research Program"},{"name":"WA I-502 funds administered through the Washington State University Alcohol and Drug Abuse Research Program"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2021,1,27]]},"abstract":"<jats:p>Contextual drug-associated memories precipitate craving and relapse in cocaine users. Such associative memories can be weakened through interference with memory reconsolidation, a process by which memories are maintained following memory retrieval-induced destabilization. We hypothesized that cocaine-memory reconsolidation requires cannabinoid type 1 receptor (CB1R) signaling based on the fundamental role of the endocannabinoid system in synaptic plasticity and emotional memory processing. Using an instrumental model of cocaine relapse, we evaluated whether systemic CB1R antagonism (AM251; 3 mg\/kg, i.p.) during memory reconsolidation altered (1) subsequent drug context-induced cocaine-seeking behavior as well as (2) cellular adaptations and (3) excitatory synaptic physiology in the basolateral amygdala (BLA) in male Sprague Dawley rats. Systemic CB1R antagonism, during, but not after, cocaine-memory reconsolidation reduced drug context-induced cocaine-seeking behavior 3 d, but not three weeks, later. CB1R antagonism also inhibited memory retrieval-associated increases in BLA zinc finger 268 (zif268) and activity regulated cytoskeletal-associated protein (Arc) immediate-early gene (IEG) expression and changes in BLA AMPA receptor (AMPAR) and NMDA receptor (NMDAR) subunit phosphorylation that likely contribute to increased receptor membrane trafficking and synaptic plasticity during memory reconsolidation. Furthermore, CB1R antagonism increased memory reconsolidation-associated spontaneous EPSC (sEPSC) frequency in BLA principal neurons during memory reconsolidation. Together, these findings suggest that CB1R signaling modulates cellular and synaptic mechanisms in the BLA that may facilitate cocaine-memory strength by enhancing reconsolidation or synaptic reentry reinforcement, or by inhibiting extinction-memory consolidation. These findings identify the CB1R as a potential therapeutic target for relapse prevention.<\/jats:p>\n                  <jats:p>\n                    <jats:bold>SIGNIFICANCE STATEMENT<\/jats:bold>\n                    Drug relapse can be triggered by the retrieval of context-drug memories on re-exposure to a drug-associated environment. Context-drug associative memories become destabilized on retrieval and must be reconsolidated into long-term memory stores to persist. Hence, targeted interference with memory reconsolidation can weaken maladaptive context-drug memories and reduce the propensity for drug relapse. Our findings indicate that cannabinoid type 1 receptor (CB1R) signaling is critical for context-cocaine memory reconsolidation and subsequent drug context-induced reinstatement of cocaine-seeking behavior. Furthermore, cocaine-memory reconsolidation is associated with CB1R-dependent immediate-early gene (IEG) expression and changes in excitatory synaptic proteins and physiology in the basolateral amygdala (BLA). Together, our findings provide initial support for CB1R as a potential therapeutic target for relapse prevention.\n                  <\/jats:p>","DOI":"10.1523\/jneurosci.1390-20.2020","type":"journal-article","created":{"date-parts":[[2020,11,30]],"date-time":"2020-11-30T19:30:32Z","timestamp":1606764632000},"page":"613-629","source":"Crossref","is-referenced-by-count":21,"title":["CB1 Receptor Signaling Modulates Amygdalar Plasticity during Context-Cocaine Memory Reconsolidation to Promote Subsequent Cocaine Seeking"],"prefix":"10.1523","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7360-8971","authenticated-orcid":false,"given":"Jessica A.","family":"Higginbotham","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0403-4956","authenticated-orcid":false,"given":"Ben D.","family":"Richardson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4016-2285","authenticated-orcid":false,"given":"Hiroko","family":"Shiina","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shi Min","family":"Tan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark A.","family":"Presker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6703-0330","authenticated-orcid":false,"given":"David J.","family":"Rossi","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":"393","published-online":{"date-parts":[[2020,11,30]]},"reference":[{"key":"2023041803450195000_41.4.613.1","doi-asserted-by":"publisher","DOI":"10.1097\/FBP.0000000000000039"},{"key":"2023041803450195000_41.4.613.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nlm.2014.09.001"},{"key":"2023041803450195000_41.4.613.3","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/4273280"},{"key":"2023041803450195000_41.4.613.4","doi-asserted-by":"publisher","DOI":"10.1002\/hipo.20420"},{"key":"2023041803450195000_41.4.613.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2006.04.017"},{"key":"2023041803450195000_41.4.613.6","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-013-3203-9"},{"key":"2023041803450195000_41.4.613.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.09.020"},{"key":"2023041803450195000_41.4.613.8","first-page":"25","article-title":"Classically conditioned responses in opioid and cocaine dependence: a role in relapse","volume":"84","author":"Childress","year":"1988","journal-title":"NIDA Res Monogr"},{"key":"2023041803450195000_41.4.613.9","doi-asserted-by":"publisher","DOI":"10.1176\/ajp.156.1.11"},{"key":"2023041803450195000_41.4.613.10","doi-asserted-by":"publisher","DOI":"10.1126\/science.1195298"},{"key":"2023041803450195000_41.4.613.11","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2008.0090"},{"key":"2023041803450195000_41.4.613.12","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-013-3331-2"},{"key":"2023041803450195000_41.4.613.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.10.018"},{"key":"2023041803450195000_41.4.613.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.09.024"},{"key":"2023041803450195000_41.4.613.15","doi-asserted-by":"publisher","DOI":"10.1126\/science.1086881"},{"key":"2023041803450195000_41.4.613.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2011.06.019"},{"key":"2023041803450195000_41.4.613.17","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5146-05.2006"},{"key":"2023041803450195000_41.4.613.18","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2007.05674.x"},{"key":"2023041803450195000_41.4.613.19","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2009.06888.x"},{"key":"2023041803450195000_41.4.613.20","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2013.05.013"},{"key":"2023041803450195000_41.4.613.21","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0799-04.2004"},{"key":"2023041803450195000_41.4.613.22","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0910338106"},{"key":"2023041803450195000_41.4.613.23","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2010.07.027"},{"key":"2023041803450195000_41.4.613.24","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2008.06.010"},{"key":"2023041803450195000_41.4.613.25","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1305235110"},{"key":"2023041803450195000_41.4.613.26","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.050187"},{"key":"2023041803450195000_41.4.613.27","doi-asserted-by":"publisher","DOI":"10.1089\/can.2016.0030"},{"key":"2023041803450195000_41.4.613.28","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2007.04.026"},{"key":"2023041803450195000_41.4.613.29","doi-asserted-by":"publisher","DOI":"10.1126\/science.1095760"},{"key":"2023041803450195000_41.4.613.30","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2005.08.007"},{"key":"2023041803450195000_41.4.613.31","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0323-06.2006"},{"key":"2023041803450195000_41.4.613.32","doi-asserted-by":"publisher","DOI":"10.1038\/220704a0"},{"key":"2023041803450195000_41.4.613.33","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.25.23.10286-10300.2005"},{"key":"2023041803450195000_41.4.613.34","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0735-14.2015"},{"key":"2023041803450195000_41.4.613.35","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2009.08.035"},{"key":"2023041803450195000_41.4.613.36","doi-asserted-by":"publisher","DOI":"10.1002\/cne.902220410"},{"key":"2023041803450195000_41.4.613.37","doi-asserted-by":"publisher","DOI":"10.1097\/00008877-200312000-00002"},{"key":"2023041803450195000_41.4.613.38","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2005.08.006"},{"key":"2023041803450195000_41.4.613.39","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1723-08.2008"},{"key":"2023041803450195000_41.4.613.40","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3273-12.2013"},{"key":"2023041803450195000_41.4.613.41","doi-asserted-by":"publisher","DOI":"10.1590\/s1516-44462009000200012"},{"key":"2023041803450195000_41.4.613.42","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-4388(97)80010-4"},{"key":"2023041803450195000_41.4.613.43","doi-asserted-by":"publisher","DOI":"10.1038\/35021052"},{"key":"2023041803450195000_41.4.613.44","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7601156"},{"key":"2023041803450195000_41.4.613.45","unstructured":"National Research Council (2011) Guide for the care and use of laboratory animals, Ed 8. Washington, DC: The National Academies Press."},{"key":"2023041803450195000_41.4.613.46","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2012.12"},{"key":"2023041803450195000_41.4.613.47","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2009.06889.x"},{"key":"2023041803450195000_41.4.613.48","doi-asserted-by":"publisher","DOI":"10.1126\/science.1239073"},{"key":"2023041803450195000_41.4.613.49","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2907"},{"key":"2023041803450195000_41.4.613.50","doi-asserted-by":"crossref","unstructured":"Rao-Ruiz P , Schmitz LJMM , Smit AB , Spijker S (2015) AMPA receptor plasticity in retrieval, reconsolidation and post-retrieval extinction of memories. In: Novel mechanisms of memory, pp 21\u201341. Cham: Springer International Publishing.","DOI":"10.1007\/978-3-319-24364-1_2"},{"key":"2023041803450195000_41.4.613.51","doi-asserted-by":"publisher","DOI":"10.1101\/lm.77504"},{"key":"2023041803450195000_41.4.613.52","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2017.09.003"},{"key":"2023041803450195000_41.4.613.53","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.12.105"},{"key":"2023041803450195000_41.4.613.54","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2017.04.037"},{"key":"2023041803450195000_41.4.613.55","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00963.2016"},{"key":"2023041803450195000_41.4.613.56","doi-asserted-by":"publisher","DOI":"10.1038\/nature17172"},{"key":"2023041803450195000_41.4.613.57","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00002.2003"},{"key":"2023041803450195000_41.4.613.58","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2016.01.043"},{"key":"2023041803450195000_41.4.613.59","doi-asserted-by":"publisher","DOI":"10.1016\/j.nlm.2013.11.013"},{"key":"2023041803450195000_41.4.613.60","first-page":"1","article-title":"Quantitative, two-color Western blot detection with infrared fluorescence","volume":"800","author":"Schutz-Geschwender","year":"2004","journal-title":"LI-COR Biosci"},{"key":"2023041803450195000_41.4.613.61","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-007-0850-8"},{"key":"2023041803450195000_41.4.613.62","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2012.06.046"},{"key":"2023041803450195000_41.4.613.63","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2017.07.018"},{"key":"2023041803450195000_41.4.613.64","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2017.05.022"},{"key":"2023041803450195000_41.4.613.65","doi-asserted-by":"publisher","DOI":"10.1101\/lm.1757410"},{"key":"2023041803450195000_41.4.613.66","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2090"},{"key":"2023041803450195000_41.4.613.67","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.10.008"},{"key":"2023041803450195000_41.4.613.68","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/j.cell.2008.10.008","article-title":"Homeostatic synaptic plasticity: local and global mechanisms for stabilizing","volume":"135","author":"Turrigiano","year":"2014","journal-title":"Cell"},{"key":"2023041803450195000_41.4.613.69","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2015.08.041"},{"key":"2023041803450195000_41.4.613.70","doi-asserted-by":"publisher","DOI":"10.1101\/lm.2273111"},{"key":"2023041803450195000_41.4.613.71","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2012.238"},{"key":"2023041803450195000_41.4.613.72","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2015.217"},{"key":"2023041803450195000_41.4.613.73","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-008-1450-y"},{"key":"2023041803450195000_41.4.613.74","doi-asserted-by":"publisher","DOI":"10.1101\/lm.039941.115"}],"container-title":["The Journal of Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1523\/JNEUROSCI.1390-20.2020","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1523\/JNEUROSCI.1390-20.2020","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,18]],"date-time":"2023-04-18T08:25:46Z","timestamp":1681806346000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jneurosci.org\/lookup\/doi\/10.1523\/JNEUROSCI.1390-20.2020"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,30]]},"references-count":74,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2021,1,27]]},"published-print":{"date-parts":[[2021,1,27]]}},"alternative-id":["10.1523\/JNEUROSCI.1390-20.2020"],"URL":"https:\/\/doi.org\/10.1523\/jneurosci.1390-20.2020","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.06.02.130419","asserted-by":"object"}]},"ISSN":["0270-6474","1529-2401"],"issn-type":[{"value":"0270-6474","type":"print"},{"value":"1529-2401","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,30]]}}}