{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T12:34:08Z","timestamp":1792154048430,"version":"4.4.0"},"reference-count":46,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,5,27]],"date-time":"2019-05-27T00:00:00Z","timestamp":1558915200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100015974","name":"Istituto di Ricerche Farmacologiche Mario Negri - IRCCS","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015974","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Addiction Biology"],"published-print":{"date-parts":[[2020,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Nicotine\u2010associated cues can trigger reinstatement in humans as well as in animal models of drug addiction. To date, no behavioral intervention or pharmacological treatment has been effective in preventing relapse in the long term. A large body of evidence indicates that N\u2010acetylcysteine (N\u2010AC) blunts the activation of glutamatergic (GLUergic) neurons in the nucleus accumbens (Nacc) associated with reinstatement. We evaluated the effect of an experimental cue exposure therapy (eCET) alone or in combination with N\u2010AC to verify whether restoring GLU homeostasis enhances extinction of nicotine\u2010associated cues. Rats were trained to associate discriminative stimuli with intravenous nicotine or saline self\u2010administration. Reinforced response was followed by cue signals. After rats met the self\u2010administration criteria, the lasting anti\u2010relapse activity of i.p. N\u2010AC or vehicle was assessed in three different experimental conditions after 14\u00a0days of treatment: treatment\u00a0+\u00a0eCET; treatment\u00a0+\u00a0lever\u2010presses extinction (LP\u2010EXT); and treatment\u00a0+\u00a0abstinence. N\u2010AC 100\u00a0mg\/kg, but not 60\u00a0mg\/kg, induced anti\u2010relapse activity that persisted 50\u00a0days after treatment only when paired with either LP\u2010EXT or eCET with the greater activity found in the latter condition. To identify potential mechanisms for behavioral results, separate groups of rats that received either N\u2010AC or vehicle\u00a0+\u00a0eCET were killed at different time points for Nacc Western\u2010blot analysis. Seven days after treatment, chronic N\u2010AC restored the expression of proteins crucial for GLU homeostasis, while at 50\u00a0days, it increased the expression of type II metabotropic GLU receptors. These results suggest that N\u2010AC treatment in combination with eCET may offer a novel strategy to prevent relapse in nicotine addiction.<\/jats:p>","DOI":"10.1111\/adb.12771","type":"journal-article","created":{"date-parts":[[2019,5,27]],"date-time":"2019-05-27T22:59:32Z","timestamp":1558997972000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Lasting reduction of nicotine\u2010seeking behavior by chronic N\u2010acetylcysteine during experimental cue\u2010exposure therapy"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2682-5583","authenticated-orcid":false,"given":"Federico","family":"Moro","sequence":"first","affiliation":[{"name":"Experimental Psychopharmacology, Department of Neuroscience Mario Negri Institute for Pharmacological Research\u2014IRCCS  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Giannotti","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology University of Colorado  Denver Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Caffino","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Biomolecular Sciences Universit\u00e0 degli Studi di Milano  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2249-4692","authenticated-orcid":false,"given":"Claudio Marcello","family":"Marzo","sequence":"additional","affiliation":[{"name":"Department of Biotechnology University of Verona  Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo","family":"Di Clemente","sequence":"additional","affiliation":[{"name":"Experimental Psychopharmacology, Department of Neuroscience Mario Negri Institute for Pharmacological Research\u2014IRCCS  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8814-7706","authenticated-orcid":false,"given":"Fabio","family":"Fumagalli","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Biomolecular Sciences Universit\u00e0 degli Studi di Milano  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Cervo","sequence":"additional","affiliation":[{"name":"Experimental Psychopharmacology, Department of Neuroscience Mario Negri Institute for Pharmacological Research\u2014IRCCS  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,5,27]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0091-3057(83)90405-7"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4603(01)00289-1"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4603(90)90045-Y"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1360-0443.2002.00205.x"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1101\/lm.1041309"},{"key":"e_1_2_6_7_1","first-page":"CD003999","article-title":"Relapse prevention interventions for smoking cessation","volume":"8","author":"Hajek P","year":"2013","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2515"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1766-07.2007"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2008.10.040"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/adb.12443"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1011265108"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.111.179317"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1360-0443.1999.9433273.x"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-012-2750-9"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/adb.12049"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-016-4315-9"},{"key":"e_1_2_6_18_1","first-page":"2007","volume-title":"The Rat Brain in Stereotaxic Coordinates","author":"Paxinos G"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-016-0231-6"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1214\/aoms\/1177729885"},{"key":"e_1_2_6_21_1","isbn-type":"print","volume-title":"How to detect and handle outliers","author":"Iglewicz B","year":"1993","ISBN":"https:\/\/id.crossref.org\/isbn\/9780873892476"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2010.07114.x"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1505-16.2016"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2001.tb02141.x"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-3057(99)00234-8"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0893-133X(01)00238-X"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-3057(01)00676-1"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-006-0522-0"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-003-1473-3"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2017.00065"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2009.07.018"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2007.06.008"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2010.88"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.116.012484"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1220591110"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2808-07.2007"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-014-3545-y"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-psych-010213-115159"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1045-08.2008"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0773-16.2016"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-21-08655.2001"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2976-15.2016"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2015.04.015"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1159\/000327682"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.13m08411"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40263-014-0142-x"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1179\/1351000215Y.0000000004"}],"container-title":["Addiction Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fadb.12771","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/adb.12771","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/adb.12771","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/adb.12771","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T21:05:58Z","timestamp":1693602358000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/adb.12771"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5,27]]},"references-count":46,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2020,7]]}},"alternative-id":["10.1111\/adb.12771"],"URL":"https:\/\/doi.org\/10.1111\/adb.12771","archive":["Portico"],"relation":{},"ISSN":["1355-6215","1369-1600"],"issn-type":[{"value":"1355-6215","type":"print"},{"value":"1369-1600","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,5,27]]},"assertion":[{"value":"2018-08-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-04-09","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-05-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e12771"}}